CN111601578A - Medical fluid transfer and injection apparatus and method with compliance monitoring - Google Patents

Abstract

Drug delivery systems, injection devices, transfer apparatus, vial carriers, and administration and transfer methods are disclosed that provide radio frequency tracking and monitoring features for tracking patient compliance.

Description

Medical fluid transfer and injection apparatus and method with compliance monitoring

Priority requirement

This application claims priority and benefit of U.S. provisional application No. 62/511088 filed on 25/5/2017. This application is hereby incorporated by reference into the entire specification, drawings and claims of each of the above applications as if fully repeated herein.

Technical Field

The present subject matter relates generally to devices and methods for administering the contents of vials, and more particularly to a single use apparatus and method that transfers and mixes the contents of one or more vials into a single use injection device for administration to a subject, such as a human.

Background

Vials are one of the preferred container closure systems used by the pharmaceutical industry due to their extensive clinical history and record of long-term stability with a wide variety of drugs. Pharmaceutical drugs include standard containers of biological agents such as vials. In addition, the industry has made a great deal of investment in stationary equipment for sterile vial filling. However, vials require that the contained drug be transferred from the vial to an injection device for delivery to a patient. New container closure systems, such as pre-filled syringes and cartridges, have been introduced that allow for the direct transfer of medication from the syringe or cartridge to the patient. Injection devices such as automatic injection devices and pens have been developed to take advantage of these newer forms of container closures. Due to uncertainties regarding long-term drug stability, and the extensive manufacturing resources already available, devices incorporating standard container closure systems such as vials, pre-filled syringes or cartridges, etc., are greatly preferred by the pharmaceutical industry by devices requiring custom forms of drug closures.

However, vials, pre-filled syringes and cartridges are not necessarily optimal containers for drug delivery devices. This is especially true in the case of delivery devices that deliver relatively large volumes of medication (2-50cc) or high viscosity (over 15cP and up to about 100 cP). Vials, pre-filled syringes and cartridges are cylinders made almost exclusively of glass, which impose design constraints on force and geometry. Typical syringes and automatic injection devices are limited in the viscosity of the drug that can be delivered, as well as by the force that can be applied to the glass container closure system. New injection devices comprising a pump for delivering insulin have been developed which use a custom made container closure, but these systems are very expensive, cannot generate large forces or pressures and are typically reusable and/or refillable.

Pharmaceutical drugs including biologies are often initially sold in lyophilized or powder form or in concentrated liquid form due to factors including stability and time to market. Such drugs packaged in liquid and powder formulations in vials can require efficient preparation prior to administration. To facilitate administration of the liquid formulation in the vial, the medicament in the vial is typically packaged with an empty syringe and a plurality of needles for aspiration out of the vial and injection into the patient. In the case of powder formulations, additional diluent or solution vials may be provided to allow reconstitution of the powder drug into a solution for injection.

The risks associated with the preparation and administration of these pharmaceutical forms are significant. They include the possibility of needle sticks during reconstitution and administration processes, as well as errors in incorrect mixing and inaccurate dose volumes or concentrations delivered. This presents a real challenge to both trained caregivers and patients preparing and receiving medications. Similar risk issues may also apply to transfers of ready-to-inject drugs that must be transferred from a vial to an injection device.

The transfer also involves removal of the drug from the vial, measurement of the correct dose, and injection to the patient using a syringe. Incomplete transfer of a full volume vial forces about 25-30% overfill of the vial and associated waste. Contamination of the drug with non-sterile ambient air injected into the vial or incorrect aseptic technique can cause contamination of the injectable drug.

In particular, on-body injection devices have been the subject of efforts to develop injection devices and methods that provide benefits such as greater comfort and less pain while providing effective subcutaneous injection.

Accordingly, there continues to be a need for new and/or improved apparatus and methods for transferring, mixing and injecting drug drugs from one or more source vials into a subject and therein.

Disclosure of Invention

The following description is for the purpose of illustration only and is not intended to be limiting. The present subject matter can be employed in a variety of devices, systems, and methods not described below.

The present subject matter is directed in part to a disposable, single use device, preferably on the body, and a method for preferably automatically mixing and/or transferring the injectate contents of one or more standard vials or syringes into an injection device, preferably upon initiation by a user, and simultaneously preferably pressurizing the injection device for subsequent automatic injection into a subject, and injecting a drug into a subject. The contents of the vial may be any suitable injection. For purposes of the present specification and claims, the terms drug, medicament, injectable, fluid, medicament, pharmaceutical, medical, fluid, etc. are used broadly and include, but are not limited to, any type of drug, therapeutic or diagnostic agent, antibiotic, biological agent, sedative, sterile water, and other injectable material, alone or in combination with one or more other injectables, and whether reconstitution or concentration adjustment or other treatment is required prior to injection.

The present subject matter includes any suitable detailed configuration of the transfer device and/or injection device, but also transfer and injection devices that are particularly useful herein in combination with the apparatus described in the following documents: U.S. patent application serial No. 61/326492 filed on 21/4/2010; U.S. patent application serial No. 13/637756 filed on 9/27/2012; and U.S. patent application No. 61/704922 filed on 24/9/2012, which is incorporated herein by reference in its entirety.

In one aspect, an injection device includes a housing having an injection cannula movable within the housing between a pre-dispense position and a dispense position. A microprocessor is also mounted within the housing. A sensor system is in communication with the microprocessor and is configured to detect when the infusion cannula is in the pre-dispense position and when the cannula is in the dispense position. A transmitter is in communication with the microprocessor and is configured to transmit data indicative of the cannula position to a remote receiver.

In another aspect, to enhance monitoring of patient compliance, a medication injection device of the type comprising a housing containing an injection reservoir and an injection needle is provided with a radio frequency tag containing data identifying the device. The tag may be an active tag or chip that signals compliance-related information such as activation of the injection device and/or completion of an injection.

In another aspect, a drug delivery system for transferring and administering an injectable liquid drug into a subject includes a transfer apparatus and an injection device, wherein the transfer apparatus includes an injection device docking station. The wireless signal transmitting unit is carried by the transfer device and/or the injection device.

In another aspect, as explained more fully below, the present subject matter is directed to systems and methods for monitoring patient compliance.

In another aspect, the delivery system transmission unit may comprise a radio frequency tag containing data identifying the system. The radio frequency tag may be an active radio frequency tag configured to signal activation of the injection device. The active radio frequency tag may also be configured to signal completion of an injection by the injection device. Further, the active radio frequency tag may be configured to send a signal to activate the injection device and stop sending a signal to complete an injection by the injection device.

In another aspect, a delivery system includes a patient module and includes an active radio frequency tag configured to transmit a signal containing at least injection device information to the patient module remote from the injection device, to receive such signal and for storing data relating to the injection device and its use.

In another aspect, the patient module may be configured to send information regarding the injection device and its use, as well as unique patient information, to a remote computer or network.

In another aspect, the drug injection device may comprise a housing containing an injection reservoir and an injection needle, the device further comprising a wireless signal transmitting unit. The transmitting unit may comprise an active radio frequency tag configured to emit a signal to activate the injection device. The active radio frequency tag may be configured to signal completion of an injection device injection. Further, the active radio frequency tag may be configured to send a signal to activate the injection device and stop sending a signal to complete an injection by the injection device.

In another aspect, the device may comprise a patient module, which may be remotely located, and the device transmitting unit or active radio frequency tag is configured to transmit a signal containing at least injection device information to the patient module, which is configured to receive such a signal and store data relating to the injection device and its use. The patient module may be configured to send information about the injection device and its use, as well as unique patient information, to a remote computer or network.

In another aspect, the drug delivery system or device may comprise a transmission unit employing bluetooth wireless technology.

In another aspect, a drug delivery system and/or device may include a sending unit configured to be removed from the device for disposal.

In another aspect, a drug delivery system and/or may include a delivery unit configured for removal to allow a majority of the delivery device to be recycled. The sending unit may be configured for removal from the transfer apparatus and/or the injection device and configured for removal from the transfer apparatus and/or the injection device to allow a majority of the apparatus and/or the device to be recycled.

In another aspect, a method for monitoring use of an injection device includes the steps of: the method includes sensing a position of a cannula of the injection device and transmitting data indicative of the position of the cannula to a remote receiver.

Turning now to a more detailed description of the subject matter of the present application and its various aspects and features, reference is first made to the accompanying drawings, which are briefly identified below.

Drawings

Examples of the subject matter of the present patent application are illustrated for purposes of illustration only and not limitation in the figures of the accompanying drawings, in which:

fig. 1 is a perspective view of a single vial system including a single vial holder, transfer apparatus and injection device system embodying the present subject matter.

Fig. 2 is a perspective view of a single vial system including a dual vial holder, transfer device and injection device system embodying the present subject matter.

Fig. 3 includes a perspective view of a single vial holder including a removable top, a cross-section of a single vial holder including a removable top, and a perspective view of a single vial holder with a removable top and a vial cap removed.

Fig. 4 includes a perspective view including a removable top and a cross-section of a dual vial holder with the removable top and vial cap removed.

Figure 5 is a cross-section of figure 2 in the region of the vial holder showing the position of the vial access member relative to the septum of the vial.

Figure 6 is the cross-section of figure 1 in the area of the vial holder showing the vial entry member piercing the septum of the vial.

Figure 7 is a perspective view of the transfer apparatus shown in figure 1 showing the vial holder and injection device receiving area.

Figure 8 is a close-up view of figure 5 showing the vial access member piercing the septum of the vial with the collapsible vial access member shield.

Fig. 9 is a schematic view of the dual vial transfer system of fig. 2 with: a first vial, a second vial, a transfer device having a first variable pressure chamber and a second variable pressure chamber, and an injection apparatus including a fluid channel.

Fig. 10 is a cross-section of fig. 2 in a pre-launch position.

Fig. 11 is a schematic view of the single vial transfer system of fig. 1 with: a dual vial, a transfer device having a first variable pressure chamber, and an injection apparatus including a fluid channel.

Fig. 12 is a cross-section of fig. 1.

Fig. 13 is a schematic view of an alternative embodiment of the dual vial transfer system of fig. 2 with: a first vial, a second vial, a transfer device having a first pressure chamber, and an injection apparatus comprising a fluid channel.

Fig. 14 is a schematic view of an alternative embodiment of the dual vial transfer system of fig. 2 with: a first vial, a second vial, a transfer device having first and second variable pressure chambers, and an injection apparatus including a fluid channel.

Fig. 15 is a schematic view of an alternative embodiment of the dual vial transfer system of fig. 2 with: a first vial, a second vial, a transfer device having a first pressure chamber, a dual lumen connector, and an injection device comprising a fluid passageway.

Fig. 16 is a cross-section of fig. 1.

Fig. 17 is a schematic view of an alternative embodiment of the single vial transfer system of fig. 1 with: a drug vial, a transfer device having a first variable pressure chamber, an injection device including a fluid passageway with a check valve and a flow restrictor.

Fig. 18 is a cross-section of fig. 2.

Fig. 19 is a cross-section of fig. 2.

Fig. 20 is a perspective view of the injection device.

Fig. 21 is a top view of the injection device showing the filling of the delivery indicator in the filled state.

Fig. 22 is a top view of the injection device showing the filling of the delivery indicator in an empty state.

Fig. 23 is a perspective view showing the bottom side of the injection device with the band and fill port attached.

Fig. 24 is a perspective view showing the bottom side of the injection device with the band separated and the fill and dispense ports exposed.

Fig. 25 is a cross-section of an injection device on the transfer apparatus.

Fig. 26 is a perspective view of the injection device attached to the skin with the safety device installed.

Fig. 27 is a perspective view of the injection device attached to the skin with the safety device removed and the button up in the pre-firing state.

Fig. 28 is a perspective view of the injection device attached to the skin with the safety device removed and the button down in the fired state.

Fig. 29 is a cross-sectional view of the injection device attached to the skin with the button up in the pre-firing state.

Fig. 30 is a cross-sectional view of the injection device attached to the skin with the button down in the first firing state.

Fig. 31 is a cross-sectional view of the injection device attached to the skin with the button down in the dispensing state.

Fig. 32 is a cross-sectional view of the injection device attached to the skin showing the tip of the delivery indicator not being triggered.

Fig. 33 is a cross-sectional view of the injection device attached to the skin showing the tip of the delivery indicator being triggered.

Fig. 34 is a cross-sectional view of the injection device attached to the skin with the button locked in the post-fired state.

Fig. 35 is a perspective view of the injection device removed from the skin with the bandage remaining on the skin.

Fig. 36 is a perspective view of the injection device with the top housing removed in the filled state.

Fig. 37 is a top view of the injection device shown in fig. 36.

Fig. 38 is a perspective view of the injection device with the top housing removed in an evacuated state.

Fig. 39 is a top view of the injection device shown in fig. 38.

Fig. 40 is a perspective view of an individual vial system in a package.

Fig. 41 is a perspective view of a single vial system in an open package.

Fig. 42 is a perspective view of an individual vial system in a package with the cap removed to reveal the contents of the package.

Fig. 43 is a perspective view of a single vial system with the vial holder removed from the package and the vial cap removed.

Fig. 44 is a perspective view of a single vial system with the vial holder fully inserted into the transfer device.

Figure 45 is a perspective view of the dual vial system showing the vial holder installed.

Fig. 46 is the top view of fig. 45 showing the volume controller in a preset state.

Fig. 47 is the top view of fig. 45 showing the volume controller in the set state.

Fig. 48 is a perspective view of a dual vial system with the volume controller removed and the vial holder depressed into the transfer device to begin the mixing and transfer process.

Fig. 49 is a perspective view of the dual vial system after completion of the mixing and transfer process, filling of the injection device, and release of the injection device removal interlock.

Fig. 50 is a perspective view of a single vial system with the injection device filled and removed from the package.

Fig. 51 is a perspective view of the injection device placed on the skin with the safety device in place.

Fig. 52 is a perspective view of the injection device placed on the skin with the safety device removed.

Fig. 53 is a perspective view of the injection device placed on the skin and the button depressed to fire the start of the injection.

Fig. 54 is a perspective view of the injection device removed from the skin after injection with the button in the locked position and the bandage remaining on the skin.

Fig. 55 is a perspective view of an injection device embodying the present subject matter.

Fig. 56 is the cross-section of fig. 55 showing the injection device with the button in the first position.

FIG. 57 is a diagram showing four stages of needle penetration into tissue including a) no contact, b) boundary displacement, c) tip insertion and d) shaft insertion (VanGerwen, D.J.Neddle-tissue interaction by experiment. Ph.D.Thesis, Delftuniversity of technology,2013.ISBN978-94-6186-238-9. Pg.11).

Fig. 58 is the cross-section of fig. 55 showing the injection device with the button in the second or dispensing position.

Figure 59 is a perspective view of a single vial transfer system in which a drug vial and an injection device are mounted embodying the present subject matter.

Fig. 60 is a cross-section of fig. 59 depicting aspects of the vial holder area showing the drug vial, the vial access member, and the extension member in a down position.

Fig. 61 is a cross-section of fig. 59 depicting aspects of the vial holder area showing the drug vial, the vial access member, and the extension member in an up position.

Fig. 62 is the cross-section of fig. 59 with the cassette and tray removed and depicting aspects of the pressure chambers and fluid channels.

Fig. 63 is a cross-section of fig. 59 depicting aspects of the vial holder area showing the drug vial, the vial access member, and the exit opening.

Fig. 64 is a cross-section of a single vial system including a single vial holder, a transfer device, and an injection device system.

Fig. 65 is a diagram of an alternative embodiment of the single vial transfer system of fig. 64 with: a drug vial, a transfer device having a first variable pressure chamber, an injection device including a fluid passageway with a check valve and a flow restrictor.

Fig. 66 is the cross-section of fig. 55 showing the adhesive/device and adhesive/skin interface.

FIG. 67 is a perspective view of the bottom of the injection device showing different areas of adhesive.

Fig. 68 is the cross section of fig. 55 showing the bulging tissue on the device with permanently attached adhesive.

Fig. 69 is the cross section of fig. 55 showing the bulging tissue on the device with multi-zone attachment adhesive.

Fig. 70 is a perspective view of the top of an alternative injection device.

Fig. 71 is a cross-section of fig. 70 showing the dislodgement sensor (dis-engagement) disengaged and the needle locked in the dispensing position.

FIG. 72 is the cross section of FIG. 70 showing the expulsion sensor engaged and the needle and button retracted to the post-firing position.

Fig. 73 is the cross section of fig. 55 showing the injection device with the button in the first or pause position.

Fig. 74 is the cross-section of fig. 55 showing the injection device with the button in the second or dispensing position.

Fig. 75 is the cross-section of fig. 55 showing the injection device with the needle retracted and the button in the up or pre-firing position.

Fig. 76 is the cross-section of fig. 55 showing the injection device with the button in the second or dispensing position.

Fig. 77 is a perspective view of a single vial transfer device.

Fig. 78 is a perspective view of the injection device.

Fig. 79 is the cross-section of fig. 78 showing the injection device with the button in the second or dispensing position.

Fig. 80 is a diagram of an alternative embodiment of the single vial transfer system of fig. 64 with: a drug vial, a transfer device having a first variable pressure chamber, an injection device including a fluid passageway with a check valve and a flow restrictor.

Figure 81 is the cross-section of figure 77 depicting aspects of the vial receiving area.

Fig. 82 is a diagram of a dual vial transfer system with: a first vial, a second vial, a transfer device having a first variable pressure chamber and a second variable pressure chamber, and an injection apparatus comprising a fluid channel.

Fig. 83 is a perspective view of an injection device with a safety sleeve attached.

Fig. 84 is the cross-section of fig. 55 showing the injection device with the button in the second or dispensing position.

Fig. 85 is a cross-section of fig. 59 depicting aspects of the vial holder area showing the drug vial, the vial access member, and the angle sensor in an open position.

Fig. 86 depicts the cross section of fig. 59 showing aspects of the drug vial, the vial access member, and the vial holder area with the angle sensor in the closed position.

Fig. 87 is a diagram of an alternative embodiment of a single vial transfer system with: a drug vial, a transfer device having a first variable pressure chamber, and an injection apparatus including a fluid passageway having a check valve.

Fig. 88 is a perspective view of a transfer device with an associated injection device embodying the present subject matter for transferring the contents of a syringe, also shown, into the injection device.

Fig. 89 is a vertical cross-section taken through the transfer and injection device with the syringe in a docking station on the transfer device.

Fig. 90 is a vertical section through a transfer and injection device with the syringe in a docking station on the transfer device and the plane of the cross-section in a different position than in fig. 89.

Fig. 91 is a perspective view of the top or exposed side of a transfer device and associated injection device for transferring the contents of a pre-filled vial, as shown in the previous figures.

Fig. 92 is a perspective view of the bottom side of the transfer device of fig. 91 showing some fluid contact surfaces and flow paths that may contact the injectate during transfer and help raise the temperature of the frozen injectate.

Fig. 93 is a horizontal cross-sectional view of the transfer device of fig. 92 showing some of the fluid channels through which the injectate moves during transfer to the injection device, and the associated channel surfaces that contact the injectate and facilitate conductive heat transfer.

Fig. 94 is a perspective view of an injection device including an Rf tag and a tag reader or interrogator.

Fig. 95 is similar to fig. 94, but shows the injection device in cross-section.

Fig. 96 is a perspective view of a transfer apparatus for transferring an injection from a prefilled source, such as a vial, to an associated injection device incorporating an Rf reader.

Fig. 97 is a cross-sectional view of the transfer device and injection apparatus of fig. 96.

Fig. 98 is an enlarged view of a portion of the cross-section of fig. 97, viewed from a different angle.

Figure 99 is a block/flow diagram illustrating a system for monitoring patient compliance employing the present subject matter.

Fig. 100 is a graph illustrating warming of a frozen drug using one of the transfer and injection devices disclosed herein.

Fig. 101 is another graph showing warming of a frozen drug using another transfer and injection device of the present application.

Fig. 102 is another graph illustrating warming of a frozen drug using another transfer and injection device of the present application.

Fig. 103 is an ultrasound image showing the subcutaneous depth of a bolus injection using a commercial infusion pump with a 9mm hypodermic needle depth.

Fig. 104 is an ultrasound image showing the depth of a bolus injection using an injection device 7 similar to fig. 56, with a needle depth of 5 mm.

Figure 105 depicts a compliance monitoring system.

Fig. 106 further depicts a compliance monitoring system.

Figure 107 illustrates further aspects of compliance monitoring using an injection device of the type described herein.

Fig. 108 is a top perspective view of a radio frequency chip in an embodiment of an injection device of the present disclosure.

Fig. 109 is a bottom perspective view of the rf chip of fig. 108.

Fig. 110 is a top perspective view of an embodiment of an injection device of the present disclosure with a safety patch installed.

Fig. 111 is a top perspective view of the injection device of fig. 110 with the safety tab removed.

Fig. 112 is a cross-sectional view of the injection device of fig. 110 and 111, showing the button in a raised, extended or up position.

Fig. 113 is a cross-sectional view of the injection device of fig. 10 and 111 showing the button in a lowered, retracted or down position.

Fig. 114 is a flowchart illustrating a process performed by a microprocessor in an embodiment of the injection device of the present disclosure.

Detailed Description

Referring to fig. 1 and 2, as set forth in more detail below, the single-use disposable single-vial transfer and injection system 1 shown in fig. 1 may include a single-vial holder 2, a transfer apparatus 3, and an injection device 7. The disposable single use dual vial mixing, transfer and injection system 4 shown in fig. 2 may include a dual vial holder 5, a transfer device 6 and an injection apparatus 7. As previously mentioned, each of these aspects has individual efficacy and may be claimed separately and/or in combination or sub-combination.

Referring to fig. 3 and 4, the single vial holder 2 is shown to include a housing 8, the housing 8 including side walls 9, end walls 10 and an aperture or viewing window 11. Alternatively, the material of the vial holder 2 may be transparent to allow visualization of the contents of the vial 12. As shown in fig. 4, housing 8 is shaped to define at least one or two or more vial receiving cavities 13 or zones for securely retaining vial 12 in each zone 13. The cavity 13 in the vial holder 5 may be sized for receiving standard injection vials 12 of different sizes, such as from 1 to 30 ml. Vials 12 may be the same size or different sizes and may contain any desired injectate 14. In the dual vial holder 5 illustrated in fig. 4, the vials may include one vial 15 of powdered, lyophilized, or liquid drug, and one vial 16 of liquid or diluent. The vial holder 5 may have the vials prepackaged and assembled therein by, for example, the pharmaceutical manufacturer, or the vials may be inserted into the vial holder 5 by the end user or by a medical professional such as a pharmacist or nurse. The vial holder 5 may have suitable markings and/or features to allow only certain vials to be assembled in a certain cavity 13. For example, a powder drug vial 15 may be inserted into a particular cavity 13 of the vial holder 5 and a diluent drug vial 16 may be inserted into another cavity 13 of the vial holder 5. An aperture or viewing window 11 in the vial holder 5 allows direct visualization of the contents 14 of the vial.

Referring to fig. 3 and 4, as a further alternative, the vial holder 5 may be a component of an individual vial holder 2, wherein each vial holder holds a single vial 12. For example, an injection manufacturer may pre-assemble a vial 12 in an individual vial holder 2, which may then be connected with the vial holder 2 of another vial 12 at the time of injection, if desired. For example, a drug manufacturer may provide a lyophilized drug 15 in its own vial holder 2 and a diluent 16, such as sterile water or saline, in a separate vial holder 2. The user or medical professional may then connect the individual vial carriers 2 as needed to form a vial carrier assembly 5 for connection to the transfer apparatus 6 shown in fig. 2.

Referring back to fig. 3, the vial holder 2 may include a removable cover 17 that generally covers and protects the ends 18 of the vials during shipping and storage. A typical standard commercial drug vial 12 includes a pierceable septum 19 in the neck of the vial for access to the vial contents 14, which is covered by a removable drug vial cap or closure 20. The removable cap 17 may be configured to engage the vial cap 20 such that removal of the cap simultaneously removes the vial cap 20 and exposes the vial septum 19 to access the contents 14 after any antimicrobial wiping of the septum 19 that may be deemed necessary by a user. The vial holder 2 may have the vial 12 recessed therein such that after the vial cap 20 is removed by the cap 17, the pierceable membrane 19 is recessed within the vial holder 2 to reduce the chance of contamination by a user prior to inserting the vial holder 2 into the transfer device 3 as shown in fig. 1. The system is applicable to both single and dual vial holders 2, 5.

Referring to fig. 3, vial holder 2 may include an interlock 27 to prevent removal of vial 12 once vial 12 is inserted into vial holder 2. This helps prevent the vial 12 from being dropped or inadvertently removed during handling.

Referring to fig. 5, the vial holder 5 may be assembled to the transfer apparatus 6 by the device manufacturer with the vial cap removed and the vials 15, 16 installed into the vial holder 5. The exposed vial septum 19 is held in close proximity to the vial access member 21, 52 prior to activation. This configuration provides convenience by eliminating the need for the user to remove the vial cap, wipe the vial top 19, and assemble the vial holder 5 to the transfer device 6 prior to use of the system 4.

Referring to fig. 6, the vial holder 2 may be packaged separately from the transfer apparatus 3. In this case, the user will remove the vial cap with the removable cap 17, wipe the vial top 19 (if needed), and assemble the vial holder 2 into the transfer device 3. As shown in fig. 6, the vial holder 2 may include a locking feature 22 that interacts with the transfer device 3 to prevent the vial holder 2 from being inadvertently pulled out of the transfer device 3 after activation by a user.

Referring to fig. 5, the vial holder 5 is preferably assembled to the transfer device 6 to configure the vials 15, 16 upside down in a vertical position. This allows any liquid 23 in the vial to communicate directly with the vial access member 21, 52 after insertion into the vial holder 5. This also forces air 24 to the top of the vial in this orientation. To facilitate the septum 19 remaining free of contamination after removal of the vial cap and prior to insertion into the vial holder 5, the exposed vial septum 19 may be recessed within the vial holder 5 to prevent accidental contact, as shown in fig. 4. This configuration is applicable to both single and dual vial holder configurations.

Referring to fig. 6, the vial holder 2 is preferably mechanically configured with an insertion feature 25 to actuate a similar on/off switch in the transfer device 3, i.e., having only two states: on and off, such as a light switch. This may prevent the user from pushing the vial holder 2 halfway into the transfer device 3 and not allow the vial access member 21 to pierce the septum 19 and allow communication between the contents 14 of the vial 12 and the transfer device 3. Additionally, the vial holder 2 may interface with an interlock 26 in the transfer device 3 to lock the vial holder 2 in the closed position after full insertion of the vial holder 2 to prevent the vial holder 2 from being removed from the transfer device 3 after insertion.

Referring to fig. 7, the transfer apparatus 3 comprises an outer housing 28 and defines a vial holder docking area or first receiving station 29 and an injection device docking station or second receiving station 30 (for a removable injection device). In the illustrated construction, the vial holder docking station 29 and the injection device docking station 30 are at opposite ends of the transfer apparatus housing 28.

Referring to fig. 7, the transfer device 3 may have an outer housing 28 integrated into the packaging 31 of the system. The outer package 31 may substantially form the bottom and side walls of the transfer device outer housing 28. All the operating steps at the moment of use of the system up to the moment of removal of the injection device may take place in this package 31. This may provide cost reduction and increase ease of use for the user. In addition, incorporating the entire transfer device 3 within the packaging 31 eliminates possible user errors that may occur if a user is required to remove the transfer device 3 from the packaging 31. The package 31 may comprise a plastic tub or tray containing the system. Further, the packaging 31 may include anything within a shipping carton 32 that contains the entire system.

Referring to fig. 7, the transfer device 3 includes a vial holder docking area 29, which may include an elongated vial access member or piercing member 21. The access or piercing member 21 may be configured as a pointed or blunt cannula or needle. Referring to fig. 8, the vial holder 5 with the vial 12 attached is shown inserted into the vial docking station 29 and the vial entry member 21 pierces the vial septum 19 to allow access to the contents 14 of the vial 12. The vial access member 21 may include a foldable seal 33 to maintain sterility of the vial access member 21 and the fluid path prior to activation. A foldable seal 33 may also be attached and sealed outside of vial 12 relative to vial access member 21 to maintain sterility prior to activation.

Referring to fig. 8, the vial access member 21 of the transfer device 3 may include a multi-lumen tube 34 to communicate with an internal fluid channel 35 of the transfer device 3. Vial access member 21 preferably includes an inlet tube 36 that allows air or fluid to enter vial 12 and an outlet tube 37 that allows air or fluid to exit vial 12. These inlet and outlet pipes 36, 37 may be separate and distinct and communicate with different fluid channels in the transferring device 3. Because of the vertical orientation of vial 12 in the inverted position, lumen opening 38 in vial access member 21 may be oriented such that inlet tube opening 36 is above outlet tube opening 37. This orientation allows for the introduction of pressurized air or fluid through the upper inlet tube 36 and the output of the vial contents 14 through the lower outlet tube 37. Further, the outlet opening 37 may be positioned near the bottom of the vial 12, adjacent the septum 19, to urge the entire contents 14 of the vial 12 into the outlet 37 and out of the vial 12.

With reference to fig. 9 and 10, the transfer device 6 is configured to perform all the necessary steps of transferring and, if necessary, reconstituting the injection agent 14 contained in the vial 15, 16 and transferring the mixture to the injection device 7, preferably automatically, after the user initiates the process. The transfer device 6 is configured and preferably includes a propulsion system or systems, such as an electrically (e.g., battery powered) or mechanically (e.g., spring loaded) actuated pump, to direct diluent from the diluent vial 16 into the injection powder vial 15 and through the transfer device 6 to direct the injection 14 into the injection apparatus 7.

Referring to fig. 9 and 10, the transfer apparatus 6 may also include a series of internal fluid channels 35 to perform any transfer, reconstitution, mixing, dilution or other processing of the injectate 14 and its transfer from the vials 15, 16 in the vial holder 5 to the injection device 7 as desired. The fluid channel 35 may comprise a flexible or rigid conduit or tube. These fluid channels 35 may also include check valves, filters, flow restrictors or other means 40 to direct the medicament from the vials 15, 16 into the injection device 7 through the transfer apparatus 6.

Referring to fig. 9 and 10, the transfer device 6 may include a variable volume pressure chamber or cylinder having a movable spring-loaded piston therein and in direct communication with the internal fluid passage 35. The chamber volume of each variable volume chamber may be defined by the chamber diameter and the position of the piston within the chamber. The first pressure chamber 41 in the transferring device 6 may preferably have an initial volume in the range of 1 to 30ml set by the manufacturer. The initial contents of the first pressure chamber 41 may preferably comprise air 45. The piston 43 can be driven by a compression spring 44 in the first pressure chamber 41, the volume of which is defined and set by the manufacturer. The spring-loaded piston 43 may be suitably sized and configured to generate a static air pressure of 1 to 50psi in the first pressure chamber 41. The volume of air 45 will depend on the diameter of chamber 41 and the stroke position of piston 43 during operation. This pressure will depend on the relative volume of air 45 displaced by the piston 43 and the force exerted by the spring 44. In other words, the force exerted by spring 44 times the area of piston 43 within chamber 41 will determine the static pressure within chamber 41. The force exerted by the spring 44 at the beginning of its maximum compression height or stroke may be much higher than the force exerted by the spring 44 at the end of its travel. The spring 44 may be suitably dimensioned to control the rate at which the air 45 is expelled from the pressure chamber 41 and thus the rate of fluid transfer in the transfer device 6. The first pressure chamber 41 is preferably configured to discharge all air 45 out of the first pressure chamber 41. Alternatively, a flow restrictor 55 in the output path 35 of the pressure chamber 41 may be used to control the rate at which air 45 is expelled from the pressure chamber 41.

Referring to fig. 9 and 10, the chamber volume of the second pressure chamber 42 may be set by the manufacturer. Alternatively, the filled chamber volume of the second pressure chamber 42 may be set by the user at the time of use using a dose selector or volume controller 48 in the range of 0.5 to 30 milliliters. The spring-loaded piston 46 in the second pressure chamber 42 may be of suitable size and configuration to generate a pressure of 1 to 200psi in the second pressure chamber 42. A dose selector or volume controller 48 allows a user to select a set dose to be injected by the injection device 7 by setting the filling volume of the chamber 42. The dose selector 48 may be of any suitable configuration. The dose selector 48 may be directly coupled to a pressure plunger assembly chamber 93 movable within the pressure chamber 42. A trigger 49 within the pressure plunger assembly 93 releases the piston 46 in the second pressure chamber 42 once the piston reaches a position corresponding to the filled volume setting. The user selects the desired dose position in the second pressure chamber 42 by moving the dose selector 48, which dose selector 48 positions the pressure chamber plunger assembly 93 to define a fill chamber volume equal to the desired injected dose. Alternatively, the position of the pressure plunger assembly 93 may already be set by the manufacturer corresponding to the delivered dose and the user operates the device without dose adjustment.

Referring to fig. 9 and 10, the transfer apparatus 6 of the dual vial system 4 for providing mixing and transfer includes a vial holder 5 with a first vial 16 and a second vial 15, a first variable volume pressure chamber 41, a second variable volume dosing pressure chamber 42, a fluid channel 35 and a check valve 40 to direct air from the first pressure chamber 41 into the first vial 16 and to direct the contents 23 of the first vial 16 into the second vial 15 and to direct the mixture 14 produced in the second vial 15 into the second pressure chamber 42, the mixture 42 then being transferred into the injection device 7.

Referring to fig. 8, upon completion of insertion of the vial holder 5 into the transfer device 6 and subsequent introduction of the vial access member 21 into the vial chamber 12 by the user through the septum 19, the pressure chamber trigger 50 as shown in fig. 10 is allowed to release.

Referring to fig. 9 and 10, release of the trigger 50 then releases the first pressure chamber spring 44, allowing advancement of the first pressure chamber piston 43 in the first pressure chamber 41 such that air 45 in the first pressure chamber 41 is forced through the inlet tube 36 of the first vial access member 21 and through the internal passage 35 in the transfer device 6 into the first vial 16. As more air 45 is forced out of the first pressure chamber 41 and through the inlet tube 36 into the first vial 16, the air 45 rises to the top of the first vial 16 due to the vertical orientation of the first vial 16 within the vial holder 5. The increased air pressure in the first vial 16 causes the fluid 23 in the vial 16 to be expelled through the outlet tube 37 of the first vial access member 21 and through the inlet tube 51 of the second vial access member 52. The fluid 23 entering the second vial 15 from the first vial 16 mixes with the contents 54 of the second vial 15 containing the liquid or powder medicament and exits through the outlet tube 53 of the second vial entry member 52 and enters the second pressure chamber 42. In the same manner as in the reconstitution configuration, the plunger 43 advancing in the first pressure chamber 41 continues to push the mixture of the first fluid 23 and air 45 through the first vial 16 into the second vial 15. The increased air pressure in the top of the second vial 15 causes the reconstituted mixture 14 in the bottom of the second vial 15 to be expelled into the second pressure chamber 42. An "air vent" or check valve 40 or other type of valve may be present on the outlet tube 53 of the second vial access member 52 to urge the entire contents 23 of the first vial 16 into the second vial 15 before the contents 14 of the second vial 15 are expelled into the second pressure chamber 42. The valve does not open until the pressure corresponding to the plunger 43 pushes substantially all of the air 45 out of the first pressure chamber 41. This ensures that the contents 54 of the second vial 15 can be sufficiently mixed with the contents 23 of the first vial 16 before the mixture 14 exits the second vial 15 and enters the second pressure chamber 42. Alternatively, a flow restrictor 55 may be used in the fluid channel 35 to delay diversion and increase mixing time.

Referring to fig. 9 and 10, the injection medicament 14 flows from the second vial 15 into the second pressure chamber 42 after reconstitution, filling the chamber 42 to the extent permitted by the position of the piston 46 selected by the user or manufacturer using the dose indicator 48 corresponding to the desired dose. When the desired volume of the second pressure chamber 42 has been reached, the second pressure chamber trigger 49 releases the spring 47 and forces the piston 46 forward, expelling the selected dose of the injectant medicament 14 under pressure into the injection device 7. Calibration of the dose volume shown on the dose selector 48 and the actual dose received by the user may be required to compensate for fluid loss in the internal passage 35 of the transfer device 6. The injection device 7 is now full and ready to be removed from the transfer apparatus 6.

Referring to fig. 11 and 12, an alternative transfer apparatus 3 is provided within a single vial system 1 that does not perform mixing but transfers only fluid 14 from a single vial 15 to an injection device 7. The alternative transfer apparatus 3 comprises a vial holder 2 with a single vial 15, a variable volume pressure chamber 56, a fluid channel 35 and a check valve 40 to direct the contents 14 from the vial 15 into the injection device 7. The inlet tube 36 of the vial access member 21 is vented to the environment 57 to allow air 58 to enter the vial 1. The outlet tube 37 of the vial access member 21 is connected to the pressure chamber 56.

Referring to fig. 11 and 12, the user fully inserts the vial holder 2 into the transfer device 3 such that the vial access member 21 is introduced through the septum 19 of the vial 15 to access the contents 14 of the vial 15. This also triggers the release of the pressure chamber trigger 59. A pressure release trigger 59 releases a plunger 60 within the pressure chamber 56 connected to a retraction spring 61. The retraction spring 61 forces the plunger 60 to retract and withdraw fluid 14 from the vial 15 and fill the pressure chamber 56. The specified amount of fluid 14 withdrawn from chamber 56 may be set by the manufacturer by limiting retraction of plunger 60. Additionally, chamber 56 may be configured to withdraw all of fluid 14 from vial 15 by retracting plunger 60 to its full stroke. Once plunger 60 reaches a set position within pressure chamber 56, it interacts with dispensing trigger 62, and dispensing trigger 62 releases dispensing spring 63 to force fluid out of pressure chamber 56 into injection device 7. A check valve 40 may be used to prevent the fluid 14 from returning into the vial 15.

Referring to fig. 13, an alternative transfer apparatus 6 for a dual vial system 4 for providing mixing and transfer includes a vial holder 5 with a first vial 16 and a second vial 15, a variable volume pressure chamber 56, a fluid passageway 35 and a check valve 40 to direct the contents 23 of the first vial 16 to the second vial 15 and the resulting mixture 14 to the pressure chamber 56. The mixture 14 is then transferred back into the second vial 15 and then into the injection device 7. In this embodiment, inlet tube 36 of first vial access member 21 is open to the environment 57 to allow air 58 to enter vial 16. The outlet tube 37 of the first vial access member 21 is connected to the inlet tube 51 of the second vial access member 52. The outlet tube 53 of the second vial access member 52 is connected to a variable volume pressure chamber 56. The fluid passageway 35 includes a check valve 40 between the first vial access member 21, the second vial access member 52 and the injection device 7.

Referring to fig. 13, the user fully inserts the vial holder 5 into the transfer device 6 such that the vial access members 21, 52 are introduced through the septum 19 of the vials 15, 16 to access the contents 23, 54 of each vial 15, 16. This also triggers the release of the pressure chamber trigger. The pressure chamber trigger releases a plunger 60 within the pressure chamber 56 connected to the retraction spring. The retraction spring forces the plunger 60 to retract and withdraw fluid 23 from the first vial 16, the fluid 23 filling the second vial 15. This filling also results in mixing of the fluid 23 from the first vial 16 and the contents 54 of the second vial 15. The resulting mixture 14 from the second vial 15 fills the pressure chamber 56 until all of the fluid 23 is removed from the first vial 16. The rate at which the first vial 16 fills the second vial 15 may be controlled using the check valve 40 or the flow restrictor 55. The amount of fluid 23 withdrawn from the first vial 16 may be set by the manufacturer in the chamber 56. Once plunger 60 in chamber 56 reaches a set position within pressure chamber 56, it interacts with a dispensing trigger that releases a dispensing spring to push fluid 14 out of pressure chamber 56 back into second vial 15. This has the advantage of allowing additional mixing of the fluid 23 from the first vial 16 and the contents 14 of the second vial 15. Once all of the fluid 14 from the chamber 56 is dispensed back into the second vial 15, the solution 14 is transferred to the injection device 7. The volume of the pressure chamber 56 may be set greater than the total fluid volume so that additional air 58 is drawn into the chamber 56. This additional air 58 may be useful in ensuring that all of the liquid 14 is transferred into the injection device 7, otherwise the liquid 14 may otherwise already be present in the fluid channel 35. A check valve 40 may be used anywhere in the fluid passageway 35 to prevent the fluid 14 from returning into the first vial 16 during transfer of the mixture 14 from the second vial 15 to the injection device 7. A flow restrictor 55 may be used anywhere in the fluid passageway 35 to control the amount of mixing time within the second vial 15 before the mixture 14 is transferred to the injection device 7.

Referring to fig. 14, an alternative transfer apparatus 6 for a dual vial system 4 for providing mixing and transfer includes a vial holder 5 with a first vial 16 and a second vial 15, a first variable volume pressure chamber 56, a second variable volume pressure chamber 42, a fluid passageway 35, and a check valve 40 to direct the contents 23 of the first vial 16 to the second vial 15 and the resulting mixture 14 into the pressure chamber 56. The mixture 14 is then transferred from the first pressure chamber 56 to the second pressure chamber 42 and then into the injection device 7. In this embodiment, inlet tube 36 of first vial access member 21 is open to the environment 57 to allow air 58 to enter vial 16. The outlet tube 37 of the first vial access member 21 is connected to the inlet tube 51 of the second vial access member 52. The outlet tube 53 of the second vial access member 52 is connected to a first variable volume pressure chamber 56. The fluid passage 35 includes a check valve 40 which is also present between the first vial access member 21, the second vial access member 52 and the second pressure chamber 42 and the injection device 7.

Referring to fig. 14, the user fully inserts the vial holder 5 into the transfer device 6 such that the vial access members 21, 52 are introduced through the septum 19 of the vials 15, 16 to access the contents 23, 54 of each vial 15, 16. This also triggers the release of the pressure chamber trigger. The pressure chamber trigger releases a plunger 60 within the pressure chamber 56 connected to the retraction spring. The retraction spring forces the plunger 60 to retract and withdraw fluid 23 from the first vial 16, the fluid 23 filling the second vial 15. The filling also results in a mixing of the fluid 23 from the first vial 16 and the contents 54 of the second vial 15. The resulting mixture 14 from the second vial 15 fills the pressure chamber 56 until all of the fluid 23 is removed from the first vial 16. The rate at which the first vial 16 fills the second vial 15 may be controlled using the check valve 40 or the flow restrictor 55. The amount of fluid 23 withdrawn from the first vial 16 may be set by the manufacturer in the chamber 56. Once plunger 60 in chamber 56 reaches a set position within pressure chamber 56, it interacts with a dispensing trigger that releases a dispensing spring to push fluid 14 out of pressure chamber 56 back into second vial 15. Once all of the fluid 14 from the chamber 56 is dispensed back into the second vial 15, the solution 14 is transferred into the second pressure chamber 42, filling the chamber 42 to the extent permitted by the piston 46 position selected by the user or manufacturer using the dose indicator corresponding to the desired dose. When the desired volume of the second pressure chamber 42 has been reached, the second pressure chamber trigger releases the second pressure chamber spring and forces the piston 46 forward, expelling under pressure a selected dose of the injectant medicament 14 into the injection device 7. A check valve 40 may be used anywhere in the fluid passageway 35 to prevent the fluid 14 from returning into the first vial 16 during transfer of the mixture 14 from the second vial 15 to the second pressure chamber 42 and the injection device 7. A flow restrictor 55 may be used anywhere in the fluid passage 35 to control the amount of mixing time within the second vial 15 before the mixture 14 is transferred to the second pressure chamber 42.

Referring to fig. 15, an alternative transfer apparatus 6 for a dual vial system 4 for providing mixing and transfer includes a vial holder 5 with a first vial 16 and a second vial 15, a variable volume pressure chamber 56, a dual lumen connector 94, an inlet fluid channel 95, an outlet fluid channel 96, and a check valve 40 to direct the contents 23 of the first vial 16 through the inlet line 95 into the pressure chamber 56 during retraction of the plunger 60 into the pressure chamber 56. Advancement of the plunger 60 after being fully retracted into the pressure chamber 56 causes the fluid contents 23 to flow from the pressure chamber 56 into the second vial 15, mix with the contents 56 of the second vial 15 and the resulting mixture 14 to flow into the injection device 7. The check valve 40 in the outlet fluid passage 96 will prevent the contents 56 of the second vial 15 from being pulled into the pressure chamber 56 during the retraction phase. The check valve 40 in the inlet fluid passage 95 will prevent the fluid contents 23 in the pressure chamber 56 from being moved back to the first vial 16 during advancement of the plunger 60. The check valves in the fluid passage 35 from the second vial 15 and the injection device 7 prevent the mixture from being transferred back from the injection device 7 to the second vial 15. The flow restrictor 55 may be used anywhere in the fluid channel 35, 95, 96 to control the rate of fluid transfer. Alternatively, the use of a dual lumen connector 94 may also be used in the same manner with a single vial transfer system 1 to remove and advance fluid in different fluid channels.

Referring to fig. 16, the pressure chamber in the above embodiments may be configured with an outlet 64 that is offset or eccentric compared to a normal syringe to take advantage of gravity. When the pressure chamber 59 is filled with liquid 14 during the transfer process, there may be some air introduced into the chamber 59 in addition to the liquid 14. During the process of discharging liquid 14 from pressure chamber 59, it may be advantageous to control the sequence when air 58 or liquid 14 is discharged from pressure chamber 59. For example, if the outlet 64 of the pressure chamber 59 is oriented downward, during the process of draining the liquid 14 from the pressure chamber 59, all of the liquid 14 drains first, then the remaining air 58 drains last, as air bubbles are directed to the top of the pressure chamber 59. Conversely, if the outlet 64 is oriented upward, during the process of discharging the liquid 14 from the pressure chamber 59, all of the air 58 is discharged first, and then the remaining liquid 14 is discharged last. This is particularly advantageous when using a hydrophobic or hydrophilic filter to remove unwanted air 58 from the tubing during transfer of the liquid to the injection device 7.

The transfer device may employ various means or processes to enhance mixing. For example, the transfer device may swirl diluent into a vial containing a drug to enhance mixing and/or may employ or introduce a mixing enhancement member, such as a dynamic or static mixer, e.g., a mixing ball, auger or propeller, vibrating syringe, or the like. These techniques may be employed in a second vial of syringes or in a single syringe. Additionally, the transfer device may have an intermediate chamber between the outlet tube of the second vial access member and the pressure chamber to allow for the enhanced mixing techniques and processes described above. The transfer device may also be configured to move the injection vials to induce turbulence and enhance mixing, such as by rotating the injection vials. Flow restrictors may be used in the air or drug path to increase the transfer time to allow better mixing.

Referring to fig. 16 and 17, another optional feature of the transfer device 3 is a filter 65 in the injectant fluid path 35 for filtering the injectant 14 to remove particulates before it is introduced into the injection apparatus 7. The filter 65 may be a membrane, a depth filter, or other suitable filtration media having a sufficiently small or effective pore size to remove unwanted particulates, which may include, but are not limited to, undissolved injectate 14 in those instances where the injectate 14 is reconstituted by the transfer apparatus 3.

Referring to fig. 16 and 17, withdrawal of the injectate from the drug vial 15 may require or be enhanced by introducing replacement air 58 into the drug vial 15. In another aspect of the present subject matter, the transfer device 3 may include a replacement air passageway or vent 66 that communicates with the interior of the vial to allow replacement air 58 to enter the vial 15 as the injection 14 is withdrawn. As previously discussed, the vial access member 29 for piercing the vial septum 19 may have an inlet tube 36 and an outlet tube 37, one for the injection 14 flowing from the vial 15 and one for the displaced air 58 flowing into the vial 15. The displacement air 58 flow path 35 in the transfer apparatus 3 may include a sterile filter 65, such as a membrane or depth filter 65 having an actual or effective pore size of about 0.22 microns or less for filtering the displacement air 58. Such a port size is small enough to prevent pathogens from being introduced into vial 15 with the displacement air 58, reducing the risk of contamination of injection 14.

Referring to fig. 16 and 17, the transfer device 3 may comprise an air remover 67 in communication with the fluid channel 35 of the injection agent 14 leading from the vial 15 to the injection means 7. Such an air remover 67 may comprise a bubble trap, other configured air gap in the fluid channel 35 of the injection agent 14 that removes air 58 from the fluid channel 35 of the injection agent 14 before the air 58 is introduced into the injection device 7. The air remover 67 may be configured with a hydrophobic filter 65 or a combination of a hydrophobic filter 68 and a hydrophilic filter 69. The hydrophobic filter 68 will allow air to be discharged from the transfer device 3 but not allow liquid 14 to pass through. The hydrophilic filter 69 will allow the liquid 14 to pass but will not allow the particles or air 58 to pass. The combination and location of the filter 69 in the fluid passage 35 preferably removes all of the air 58 during the transfer process.

With reference to fig. 18 and 19, the transfer device 6 may also have additional features as well as those described above. One such feature is an interlock 70 between the dose selector 48 and the vial docking station 29. This may be, for example, a mechanical interference member 97 that prevents the user from loading the vial into docking station 29 until a dose is selected. Mechanically, the dose selector 48 may be linked to an interference member 97 at the docking station 29, which is normally in an anti-loading position to prevent insertion of the vial holder 5 into the vial holder station 29 unless moved to the load-allowing position when the dose member 48 is moved to the dose selection position. Of course, for administering an injection from a vial containing a single dose of injection or a single vial (all of which are to be injected), the transfer device need not include dose selection capability.

Referring to fig. 18 and 19, the transfer apparatus 6 may include an interlock 71 between the transfer apparatus 6 and the injection device 7 to prevent the injection device from being removed prior to filling and to indicate when the injection device 7 is ready to be removed from the transfer apparatus 6. Mechanically, the locking pin 72 may be linked to the injection device 7 to prevent removal before the injection device 7 is completely filled by the transfer apparatus 6. The locking pin 72 may be part of the transfer device 6 and communicate with the piston in the pressure chamber 42. When the pressure chamber 42 has expelled all injectate 14, this may mechanically trigger the locking pin 72 to move away from the injection device 7, allowing the injection device 7 to be removed from the transfer apparatus 6 by the user.

Referring to fig. 18, the transfer apparatus 6 may comprise an interlock between the transfer apparatus 6 and the injection device 7 to control how the injection device 7 is removed from the transfer apparatus 6. Mechanically, a flange or other protrusion 73 on the injection device 7 may mechanically interface with an undercut in the transfer apparatus 6. This configuration may allow unidirectional rotation of the injection device 7 relative to the transfer apparatus 6 for removal by the user.

Referring to fig. 18 and 19, the transfer device 6 may comprise a locking feature that prevents the injection means 7 from being activated when docked on the transfer device 6. For example, a mechanical interference member, such as a locking pin, arch or other device 72, may extend out of the transfer apparatus 6 and mechanically lock the injection device 7 in an upper position at an actuator or button. Alternatively, the mechanical interference member 72 may be a shield covering the entire injection device 7 to prevent access to the injection device 7 when on the transfer apparatus 6. The arch structure or shield 72 may be part of the transfer device 6 and communicate with the pressure chamber 42. When the pressure chamber 42 has expelled all of the injectant 14 into the injection device 7, this can mechanically trigger the dome or shield 72 to unlock the injection device 7 and move away from the injection device 7. This allows access to the injection means 7 and removal from the transfer device 6 by the user.

Another optional feature on the transfer apparatus is a quick release fill port or access member feature between the transfer apparatus and the injection device to allow quick release of the injection device from the transfer apparatus and prevent the injection device from being reattached to the transfer apparatus. After the injection device is filled and ready to be removed from the transfer apparatus, the user may remove the injection device. The filling tube or access member 83 of the transfer device may be spring loaded such that the filling tube 83 springs down into the transfer device when the injection means is removed from the transfer device. This allows for a quick release of the tube 83 from the filling port 81 of the injection device, preventing accidental leakage of the injection device at the filling port 81. This also makes the filling tube 83 inaccessible to the user, thus preventing the injection device from being reattached to the transfer apparatus.

Referring to fig. 18, the injection device 7 and the transfer apparatus 6 are preferably configured for removable attachment of the injection device 7. In the present embodiment, after the injection fluid 14 is transferred from the second pressure chamber 42 within the transfer apparatus 6 into the injection device 7 and the interlock 71 on the transfer apparatus 6 is released, the injection device 7 is ready to be detached from the injection device docking station 30 of the transfer apparatus 6 for application to the skin of the subject. As previously mentioned, alternative embodiments described herein include the transfer of injection fluid directly from a single pressure chamber to the injection device.

Referring to fig. 20, the injection device 7 may be of any suitable configuration. As previously explained, the injection device may advantageously utilize one or more of the features of the injection device described in U.S. patent application serial No. 61/326492 filed on day 4 and 21 2010, U.S. patent application serial No. 13/637756 filed on day 9 and 27 2012, and U.S. patent application No. 61/704922 filed on day 9 and 24 2012, all of which are hereby incorporated by reference.

Referring to fig. 20-22, the injection device 7 has a generally low profile, disc-shaped outer housing 74 with an upper surface 75 and a lower surface 76, through which generally low profile, disc-shaped outer housing 74 the injection needle or cannula protrudes when actuated by a user. The upper surface 75 has an actuator or button 77 for initiating an injection and also has a transparent portion 80 of the housing 74, the transparent portion 80 allowing the subject or medical professional to view the expandable member 78 to determine the amount of injection fluid 79 in the device 7. For example, the user may determine whether an injection has begun or ended. More preferably, the expandable member 78 and/or the transparent portion 80 of the housing 74 may be graduated, such as by line markings 127 or the like, so that the patient or medical professional can visually determine the amount of injection fluid 79 remaining with greater accuracy, such as, for example, about 50% complete or about 75% complete. Further, the expandable member 78 may itself include or interact with features on the outer housing 74 to show the amount of injection fluid 79 remaining. For example, the transparent portion 80 may show a color, such as, but not limited to, green, when the injection device 7 is filled with the drug 79. The transparent portion 80 may show a different color, such as, but not limited to, red, when the injection device 7 is emptied of the drug 79. In the middle of the assignment, the transparent portion 80 may show a combination of colors.

Referring to fig. 23-25, the lower surface 76 of the injection device 7 includes a fill port 81 and a dispense port 82. The fill port 81 is an interface that allows a transfer device fill tube 83 to transfer the liquid 79 to the injection device 7. The dispensing port 82 also contains an internal passage 84 between the injection agent 79 expelled from the expandable member 78 and the needle 85. The fill port 81 and the dispense port 79 may be in direct fluid communication through the internal passage 86, or they may be combined into a single port.

Referring to fig. 23-25, the injection device may preferably include a fill port 81, the fill port 81 including a check valve 87 to prevent leakage of the pressurized injection agent 79 from the injection device 7 when the injection device 7 is removed from the transfer apparatus 6 and the fill port 81 is removed from the fill tube 83.

Referring to fig. 23-25, the injection device 7 may also have a fill port 81 configured to accept insertion of a syringe. The syringe may be configured with a luer fitting or a needle. The filling port 81 is configured to allow manual filling of the injection device by a user. The transfer device 6 may still be used but would not be needed in this configuration.

Referring to fig. 23-25, the injection device 7 may also have a dispensing port 82 configured to connect directly to an intravenous cannula via an attached tube or standard needle port.

Referring to fig. 23-25, the lower surface 76 of the injection device 7 carries an adhesive 88 for temporarily securing the injection device 7 to the subject's skin until injection is complete. During removal of the injection device 7, the adhesive tape liner 89 may be automatically removed to expose an adhesive surface 88 on the lower surface 76 of the injection device 7 that may be used to adhere the injection device 7 to the patient's skin. Alternatively, the tape backing 89 may have a tab 90, which the user may pull on the tab 90 to manually remove before adhering the injection device 7 to the skin. Alternatively, the tab may be attached to a surface of the transfer device 4 such that the tape pad is automatically removed when the injection device 7 is removed.

Referring to fig. 23-25, the injection device 7 may have an adhesive tape flange 91 that extends beyond the bottom surface base 76. This flange 91 of the adhesive strip 88 may act as a strain relief between the injection device 7 and the skin surface, reducing the risk of accidental dislodging (disrodinging) of the injection device 7 from the skin. In other words, similar to the tapered strain relief on the lead where it enters the connector, the extended adhesive flange 91 acts to distribute the load across the connection point between the adhesive strip 88 and the bottom base 76 of the injection device 7 to reduce any stress rise (riser) at the interface of the adhesive strip 88 and the skin.

Referring to fig. 23-25, the injection device 7 may be configured with a tapered underside surface 98, which tapered underside surface 98 presses on the adhesive flange 91 to securely attach the adhesive strip 88 to the skin without additional user intervention as the user secures the injection device 7 to the skin. By using the compliance of the human skin when pressing the injection device 7 against the skin, the tapered bottom side surface 98 of the injection device 7 effectively presses the flange 91 of the adhesive tape 88 against the skin but the exposed upper surface portion of the flange 91 is free of exposed adhesive and is therefore not attached to that portion of the tapered bottom side surface 98. The user does not need to have his fingers around the flange 91 to secure the injection device 7 to the skin, making the method of adhesive tape 88 attachment simpler.

Referring to fig. 23-25, the injection device 7 may have an underside surface 76 that is flexible or compliant instead of rigid to allow for improved attachment by conforming the injection device 7 to the skin during application.

Referring to fig. 26-28, after the injection device 7 is placed against the skin 99 or adhered to the skin 99, the safety mechanism or locking mechanism may be automatically released and the injection device 7 is ready to fire (inject). In other words, the injection device 7 is prevented from being actuated (it is locked) until it is placed against the skin. Alternatively, the user may manually remove the safety device 100, such as a safety pin, safety sleeve or collar to release the injection means in preparation for firing (injection). The injection device 7 cannot preferably be fired until the safety mechanism 100 is released. The safety mechanism 100 may be passive or active and be triggered manually by a user or automatically by the injection device 7.

Referring to fig. 26-28, the injection device 7 may use the actuator or button 77 and the visual indicator 101 in combination to define the state of the injection device 7 after it has been removed from the transfer apparatus. For example, when the button 77 is in the up position and the indicator 101 has a color such as, but not limited to, green, this may indicate that the injection device 7 is ready to start an injection. In addition, the button 77 may have a sidewall 102 that is a different color than its top 103. When the button 77 is depressed, the user cannot see the sidewall 102 of the button 77; this may indicate that the injection device 7 is being used. The injection means 7 may alert the user when the injection of the medicament is completed. The warning will be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination. The button 77 is desirably designed to give the user audible, visual, and tactile feedback when the button 77 "pops up" to the locked position. The injection device 7 may indicate to the user that it has completed dispensing and that a full dose has been delivered to the patient when the button 77 is in the up position and the indicator window 101 shows that the injection device is empty. For example, when the button 77 is in the up position and the indicator 101 shows a different color, such as, but not limited to, red, this may indicate that the injection device 7 has completed an injection.

Referring to fig. 29-31, the injection device 7 may have an actuator or button 77, the user depressing the actuator or button 77 on the injection device 7 to initiate an injection. The button 77 may be configured as an on/off switch, i.e., having only two states, on and off, such as a light switch. This prevents the user from pushing the button 77 halfway and not activating the injection device 7. Once activated, the "light switch" type button 77 can quickly insert the needle 85 into the skin 99 independent of user manipulation of the button 77. Alternatively, the button 77 may have a continuous motion, allowing the user to slowly insert the needle 85 into the skin 99. The button 77 may be coupled directly to the needle 85, preferably by using an adhesive 104, creating the button 77 and the needle 85.

Referring to fig. 29-31, the injection device 7 can advance the needle 85 into the skin 99 upon actuation of the button 77, the button 77 initially advancing to a first position or depth (as shown in fig. 30) and preferably automatically retracting slightly to a second position or depth (as shown in fig. 31). The first depth in fig. 30 is achieved by an over travel (override) of button 77 during actuation. The first depth may be controlled by a feature 105 in the button 77 in direct contact with a base 106 of the injection device 7. The final depth of the needle 85 is suitable for subcutaneous injection. Alternatively, for intradermal injections, the final depth of the needle 85 may be reduced. Alternatively, for intramuscular injection, the final depth of the needle 85 may be increased. Upon reaching the first depth, the needle 85 is retracted back to the second depth, as shown in FIG. 31. The retraction distance of the needle to the second depth is in the range of 0.1-2 mm. This retraction feature is preferred to prevent the needle 85 from being blocked by tissue during the initial insertion process. This tissue blockage may require a very high pressure to overcome and prevent the injection device 7 from delivering the drug. Retraction of the needle 85 from the first position to the second position creates an open pocket in front of the needle tip 107, allowing reduced pressure for initiating flow of the medicament from the needle 85. The reduced pressure for initiating the flow of medicament from the needle is preferred for the injection device 7 to maintain a relatively constant pressure during injection.

Referring to fig. 29-31, the injection device 7 may include a needle 85 with a side aperture 108. As shown in fig. 31, once the button 77 on the injection device 7 is fully depressed, the needle 85 will be fully inserted through the dispensing port 82 into the skin 99 and the injection device 7 will begin dispensing the injectate. Until button 77 is fully depressed, side hole 108, and therefore the internal lumen of needle 85, is not in communication with fluid passageway 86 of dispensing port 82. Both the side hole 108 and the needle tip 107 are retained within the septum 109. With the side hole 108 and needle tip 107 held within the septum 109, the entire drug path remains sterile until the time of use. When the button 77 is fully depressed and the needle 85 is in the dispensing position, the side hole 108 in the needle 85 communicates with the fluid passage 86 of the dispensing port 82 and liquid injection begins.

Referring to fig. 29-31, septum 109 provides the advantage of sealing needle tip 107 and side aperture 108 to block injectate before and after dispensing. The needle tip 107 and the side hole 108 of the sealing needle 85 at the end of the injection has the particular advantage of preventing the injection agent from dripping from the injection device 7 after the end of the dispensing and/or after its removal from the skin surface. It also prevents contaminants from entering the hollow needle before it is actuated to the skin. The septum 109 may be made of any suitable material to allow sealing once the needle 85 has pierced it. The material composition of the diaphragm 109 may preferably be silicone. Alternatively, the material composition of the separator may also be a mixture of different materials, including but not limited to bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, natural rubber and silicone. Alternatively, the fluid channel 86 including the dispensing port 82 may be a rigid plastic with injection molded silicone to create the previously described septum.

Referring to fig. 29-31, the septum 109 at the dispensing port 82 may protrude slightly from the underlying surface of the injection device 7 into the skin surface 99 to provide pressure on the skin surface 99 at the injection site. This pressure exerted by the dispensing port 82 on the skin surface 99 after needle retraction can eliminate the situation where the injection comes out of the injection site, commonly referred to as blowback.

Referring to fig. 29-31, the injection device 7 may include a set of spring tabs 110 that interact with the button 77 to perform a locking function. Spring tab 110 is biased to lock into an undercut 111 in button 77 to hold button 77 in the first upper or pre-firing position, as shown in fig. 29. The geometry of the undercut 111 and the spring tab 110 help to generate the previously described lamp switch actuation force. The lamp switch actuation is achieved by the button 77 translating relative to the spring tab 110 and mating the geometry of the undercut 111 surface.

Referring to fig. 29-31, the injection device 7 may include a spring tab 112, the spring tab 112 interacting with the button 77 in the injection device 7 to perform a locking function such that when the button 77 is actuated to a first depth and retracted slightly to a second depth or dispensing position, an undercut feature 113 in the button 77 allows the spring tab 112 to retain the button 77 in the dispensing position until the injection device 7 has completed dispensing.

Referring to fig. 32-33, the injection device 7 may include a tip that delivers an indicator or purge indicator 114 to sense when all of the fluid 79 has been expelled from the expandable member 78 and when the injection device 7 has completed dispensing. The evacuation indicator 114 may be configured with a slot or other opening 115 to slide over the expandable member 78 at the exit opening when the expandable member 78 is in the deflated state after all fluid has been expelled. There may be two states of the purge indicator. As shown in fig. 32, the evacuation indicator may be in a first position or biased out of the state when the expandable member 78 is filled with fluid 79 at this portion and is not contained within the slot or opening 115. This first position will translate to the non-deflated state of the expandable member 78 when the diameter of the expandable member 78 is greater than its minimum due to the contained residual fluid 79. As shown in fig. 33, the evacuation indicator 114 may be in a second position or biased state when the expandable member 78 is partially or fully contained within the slot or opening 115. When the diameter is at a minimum, the second position will translate to an evacuated state of the expandable member 78.

Referring to fig. 32-33, the injection device 7 may include an automatic needle retraction mechanism at the dispensing end. The mechanism includes a direct coupling between the spring tab 112, the button undercut feature 113, and the purge indicator 114, as previously mentioned. When the expandable member 78 is filled with the injection agent 79 and the button 77 is pressed from the first pre-firing position to the second dispensing position, as shown in fig. 33, the undercut features 113 in the button 77 allow the spring tabs 112 to hold the button 77 in the dispensing position until the injection device 77 has completed dispensing. The spring tab 112 may also be directly coupled to the empty indicator 114, which is naturally in the first position or biased state. The movement of depressing the button 77 to the second or dispensing position allows the post feature 116 in the button 77 to provide a bias or pre-tension on the spring tab 112 to urge the purge indicator 114 to its second or biased state. However, because the expandable member 78 is initially large in diameter and filled with the injection agent 79, the purge indicator 114 cannot be moved to the second position or biased-in state as shown in FIG. 32. After the button 77 is depressed, the fluid 79 begins to exit the expandable member 78 through the needle, as previously mentioned. Once the expandable member 78 has expelled all of the fluid 79 and is at the minimum diameter, the purge indicator 114 (under pre-tension from the spring tabs 112) will move to the second position or biased state, as shown in FIG. 33. The spring tabs 112 that are directly coupled to the empty indicator 114 also move with the empty indicator 114. This movement releases the spring tab 112 from the undercut feature 113 in the button 77 to allow the button 77 (and needle) to move upward to the final or post-firing position after dispensing is complete as shown in fig. 34.

Referring to fig. 34, locking spring tabs 117 may also interact with button 77 in injection device 7 to perform a locking function such that button 77 is released when the injection is completed and button 77 is urged upwardly by return spring 118 to an upper-most or post-fired position. The height of the button 77 relative to the top of the injection device 7 in the upper most or post-firing position (shown in figure 34) may be higher than in the pre-firing position (as shown in figure 29). The tip of locking spring tab 117 moves outward to the outer diameter surface 119 of button 77 within outer housing 74 to lock button 77 in the up or post firing position and prevent button 77 from being actuated again.

Referring to fig. 34, the injection device 7 may include a return spring 118 that interacts with the button 77 to provide biasing of the button 77 to a first, upper or pre-firing position. When the button is actuated downward to a second depth or dispensing position, the return spring 118 is compressed, causing more bias or preload. At the end of the dispense period, button 77 is unlocked from the second depth or dispense position (shown in fig. 31) to move up to the last or post-fire position after dispensing is complete as previously mentioned. The bias of the return spring 118 forces the button 77 upward to a final or post-firing position.

Referring to fig. 34-35, upon removal of the injection device 7 from the skin 99, the injection device 7 will preferably be locked, preventing non-destructive access to the needle or reuse of the injection device 7. The injection device 7 may indicate to the user that a full dose has been delivered. The indication may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination.

Referring to fig. 35, upon removal of the injection device 7 from the skin 35, the bandage 120 may be released from the injection device 7 and retained on the skin surface 35. This can be influenced by using an adhesive on the bandage portion that attaches the bandage to the skin more strongly than the adhesive that attaches the bandage to the injection device 7. Thus, when the housing is lifted from the skin, the bandage 120 remains in place over the injection site, as described in U.S. patent application No. 12/630996 and U.S. patent No. 7637891 filed 12-4-2009, which are incorporated herein by reference.

Referring to fig. 36-39, the injection device 7 may preferably include a manifold 121, the manifold 121 being assembled to both the expandable member 78 and the fill port 81 and the dispensing port 82, and providing direct fluid communication between the expandable member 78 and the fill port 81 and the dispensing port 82 of the injection device 7. The manifold 121 may be configured at the end assembled to the expandable member 78 that is assembled to the expandable member 78 such that it is large in diameter to facilitate all of the fluid 79 to fill and drain the expandable member 78, as previously discussed. The manifold 121 may preferably include internal passages 122 to allow fluid to flow into and out of the expandable member 78. The manifold 121 may be configured with a filter 123 in the injectate fluid passage 122 for filtering the injectate 79 to remove particulates before and after it is introduced into the expandable member 78. The filter 123 may be a membrane, a depth filter, or other suitable filtration media having a sufficiently small pore size or effective pore size to remove unwanted particulates that may include, but are not limited to, undissolved injectate 79 in those instances where the injectate 79 is reconstituted by the transfer apparatus. The manifold 121 may also be configured with a filter 123 for removing air. Such air removal filters 123 may include bubble traps, air gaps of other configurations in the injectate fluid passage 122 that remove air from the injectate fluid passage 122 before the air is introduced into the expandable member 78. The air removing filter 123 may be configured with a hydrophobic filter or a combination of a hydrophobic filter and a hydrophilic filter. The hydrophobic filter will allow air to be discharged from the transfer device but not liquid to pass through. A hydrophilic filter will allow liquid to pass but not particles or air. The air removal filter 123 may also have a check valve to allow for the discharge of trapped air. Alternatively, the air remover and filter 123 may be located at any point in the fluid path from the fill port 81 to the needle 85. For example, the most downstream point in the fluid passageway is the distal end 128 of the expandable member 78. The inner mandrel 124 may be connected to the distal end 128 of the expandable member 78. An air remover or filter 123 may be integrated into this downstream point to allow trapped air to be vented during filling of the injection device 7. In addition, the mandrel 124 may include a slot along its length that communicates with the downstream filter 123 to assist in the discharge of air during the filling process.

Referring to fig. 36-39, the injection device 7 may include an elastic expandable member 78, such as an elastomeric balloon or bladder. The material composition of the expandable member 78 may preferably be silicone. Alternatively, the material composition of the expandable member 78 may also be a mixture of different materials including, but not limited to, bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, natural rubber, and silicone. In addition, the expandable members 78 may be coated to improve their surface properties. The coating may include parylene, silicone, teflon, and fluorine gas treatment. Alternatively, the expandable member 78 may be made of a thermoplastic elastomer.

Referring to fig. 36-39, the injection device 7 may include an elastically expandable member 78 into which an injection 79 is transferred under pressure. This causes the expandable member 78 to enlarge and the elasticity of the expandable member 78 creates a pressure force that tends to expel the injection 79. The pressure chamber of the previously described transfer device (or such other pump or pressurizing means as may be used in the transfer device) transfers the injectant 79 under pressure to the injection means 7. Introduction of the injection agent 79 under pressure into the expandable member 78 causes it to stretch and expand in diameter and length. An example of this would be blowing up a long, thin balloon. The volume of the injection device 7 may range from 0.5 to 30 mm. When inflated, the resilient inflatable member 78 exerts a jet pressure in the range of 1 to 200psi on the injection 79 contained in the inflatable member 78, so that the injection device 7 is ready to automatically administer the injection 79 when it is pressed by the user by depressing the button as described previously. Thus, the transfer device as described before not only operates to transfer (and if necessary mix, dilute and filter) a measured amount of the injection agent 79 to the injection device 7, but also simultaneously fills or provides motive pressure (by inflating the elastic expandable member 78) to the injection device 7 so that the injection device 7 is ready to automatically dispense the injection agent 79 under the pressure exerted by the elastic expandable member 78 when actuated by a user.

This aspect of the transfer apparatus (simultaneous transfer and filling) is particularly advantageous. Although the above application shows the injection device 7 in a pre-filled or filled condition for injecting the medicament 79 when the injection device 7 is actuated, the present disclosure contemplates that the injection device 7 may remain empty and the expandable member 78 in a more relaxed and unfilled condition, i.e., in an unfilled or unfilled condition, until administration of the injection 79 is desired. Only then, the injection agent 79 is mixed or processed as required and introduced into the injection device 7, inflating the expandable member 78 to the filled condition. In the present disclosure, the drug is stored in its initial container closure (vial) until the time of use. Since the injection 79 will typically be injected within a few seconds to a few hours after transfer from the vial to the injection device 7, shelf life and material compatibility of the drug with the material in the fluid channel within the injection device 7 is not a significant issue. The challenges and costs of designing the injection device 7 and selecting materials for extended shelf life of the pre-filling injection device 7 are significantly reduced.

With reference to fig. 36-39, the present subject matter may use the features of the injection device 7 described in the patent applications previously described herein incorporated by reference. However, the expandable member 78 used in the injection device 7 may here also preferably take the form of an elongated balloon or sac arranged in a planar spiral or helical configuration as illustrated. As previously mentioned, the injection device 7 includes a circular shaped outer housing 74 having a helical slot or recess 125 formed therein. The elongated balloon or bladder 78 rests in the slot 125 with one end for direct or indirect communication with the injection needle 85 through the fluid passage 122 and the other end for direct or indirect communication with the dispensing indicator 101. The elongated helical configuration allows the balloon or bladder 78 to have a substantial volume for such an amount of injection 79, as may be desired, while also contributing to the low profile construction of the injection device 7. In other words, by utilizing a relatively long expandable member 78 having a large length to diameter ratio, very high pressures and volumes can be achieved with minimal force required. Additionally, the volume of the expandable member 78 may be varied by varying the fill length without significantly altering the pressure/volume curve of the expandable member 78.

Referring to fig. 36-39, one of the other aspects described in U.S. patent application No. 61/704922 filed on 24/9/2012 that may be employed in the present subject matter is the use of an insert or plug or mandrel 124 within the expandable member 78 to pre-stress the expandable member 78 to a slightly expanded position when unfilled, such that when the expandable member 78 expels the injection 79, it will contract or collapse to a condition in which it is still stretched or stressed and continues to exert pressure on any fluid therein, as shown in fig. 38 and 39. This better ensures that all or substantially all of the injectant 79 is completely expelled from the injection device 7. The mandrel or shaft 124 may be a fluid-filled expandable member, if desired. This would allow for a variable size mandrel 124. Alternatively, the expandable member 78 may have a sufficiently small internal volume (small diameter) when unstressed such that virtually all of the injectate 79 is expelled without the need for an internal mandrel or shaft 124. Additionally, the expandable member 78 may be flattened/stretched by "wrapping" it around a surface (such as the cylindrical wall 134) within the injection device. The pre-stress created in the expandable member 78 may act to eliminate any residual fluid volume remaining therein.

There are a number of different ways to expand and/or contract the expandable member 78 in the arcuate manner previously described. Referring back to fig. 34, one way is to design the expandable member 78 with a thicker wall cross-section 126 in one area around the circumference of the expandable member 78, which will cause the expandable member 78 to expand in a circular manner. Alternatively, the separation member 126 may be fixed along the length of the expandable member 78 to effectively stiffen the expandable member 78 in that portion of the circumference that will cause the expandable member 78 to expand in an arcuate manner. Referring back to fig. 36, another way is to use an internal feature such as a slot or recess 125 in the housing 74 of the injection device 7 to guide the expandable member 78 around a circular or helical path. These features 125 may interact with the expandable member 78 in a number of ways, the simplest being that the profile of the expandable member is limited by a slot 125 in the housing 74 of the injection device 7. Friction between the expandable member 78 and the inner surface 125 of the housing 74 may be reduced by lubricating the outer side surface of the expandable member 78 or by inserting the expandable member 78 into a low spring rate spring that will limit both the friction and the outer diameter of the expandable member 78 without limiting the length.

Referring to fig. 36-39, the elongated expandable member 78 may preferably be configured to expand along an arc having a predetermined tube diameter without the aid of a wall or guide within the injection device. Referring back to fig. 34, looking at the cross-section of the elongated expandable member 78, a thicker wall region 126 in a small portion of the circumference of the expandable member 78 may be added to expand the elongated expandable member 78 in the arc previously described. The arcuate expandable member 78 increases in length due to the increase in pressure and volume therein; the thicker portion 126 deflects less than the thinner portion.

Referring to fig. 36, the arcuate expandable member 78 will expand in length in the shape of a circular arc to direct its heavy wall thickness region 126 or less deflected region to the inside of the circle. Increasing the wall thickness 126 of the expandable member 78 within a small area 126 around the circumference will effectively continue to decrease the radius of the arc of the expandable member 78. The increase in wall thickness 126 may be accomplished by molding or extruding it into the arcuate expandable member 78 or by incorporating a strip of material into one side 126 of the expandable member to lengthen that portion of the wall 126 at a slower rate to expand the expandable member 78 in the arc shape previously discussed.

Referring to fig. 37, the distal end of the expandable member 78 may be secured with an element such as an indicator 101 that is constrained to follow a guided path within the inner surface 125 of the housing 74. Alternatively, the expandable member 78 may be pre-stretched and flattened following the circular diameter (such as the wall 134) inside the injection device 7 without a change in the expandable member length. Alternatively, a straight or curved mandrel 124 (having a length greater than the unstressed expandable member) may be used to stretch the expandable member to a circular shape within the injection device 7 prior to filling. Alternatively, the spindle 124 may be used as a visual indicator to show the status of the injection device 7 and the progress of the injection. The mandrel 124 may be tinted to allow it to be easily viewed through the housing.

Referring to fig. 36-39, an injection agent 79 is injected into the expandable member 78 by the transfer device and the expandable member 78 is expanded to a certain outer diameter controlled by the configuration of the inner surface 125 of the housing 74. In this way, the entire length of the expandable member 78 may be filled with a known volume of drug, and the outer diameter is known at each longitudinal location along the expandable member 78. It is desirable to fill and empty the expandable member 78 along its length from end to end in a controlled manner to facilitate complete emptying of the expandable member 78 and to allow for easy and accurate measurement of the fluid 79 in the expandable member. To visually assist in determining how much fluid 79 is in the expandable member 78, graduated markings may be printed on the expandable member 78, similar to a syringe, to indicate the volume remaining in the expandable member 78. As previously described and with reference to fig. 21-22, the expandable member 78 and the housing 74 may be transparent to allow the user to view the medicament 74 and the volume remaining in the injection device 7. Alternatively, graduated markings 127 may be printed on the housing 74 to indicate the volume remaining in the expandable member 78.

Referring to fig. 36-39, in accordance with aspects of the subject matter described above, the injection agent 79 is preferably progressively expelled from the distal end 128 toward the proximal end 129 of the elongate expandable member 78. The proximal end 129 of the expandable member is adjacent the dispensing needle 82 or cannula. This allows the user to visually determine or estimate the injection status either visually alone or with the aid of the scale markings 127, window 80 or expandable member 78 on the injection housing 74. Progressive expulsion can be achieved in various ways. For example, injectate 79 exits the expandable member 78 at the manifold 121 at the proximal exit portion 130 and is preferably located at the proximal end 129 of the elongated expandable member (e.g., balloon or bladder). The thickness of the wall of the expandable member 78 may be varied (uniformly or stepwise increased) along its length from the distal end 128 toward the proximal end 129. Being constrained by the walls of the helical passage 125 in which the expandable member 78 is located, the expandable member 78 will be expanded to a substantially uniform diameter along its length with an injection 79. However, the thicker wall of the distal end 128 of the expandable member 78 will exert a greater contraction on the injectant 79 than the thinner wall at the proximal end 129 and thus will initially collapse or contract in diameter during expulsion of the injectant 79. The expandable member 78 will then progressively collapse from the distal end 128 toward the proximal end 129 as the wall of the expandable member 78 thins in that direction along its length. Because the thickness of the expandable member 78 preferably increases substantially uniformly from the proximal end 129 toward the distal or closed end 128, the force of contraction of the walls of the expandable member 78 will increase substantially uniformly along the length of the elongated expandable member 78 from the proximal bore end 129 to the distal or closed end 128 when expanded. Thus, as the injection 79 is expelled into the subject, the expandable member 78 will progressively collapse in diameter and contract in length, which preferably can be observed by the user, as described above. The distal end 128 of the elongated expandable member may allow for a movable indicator feature 101 attached in the injection device 7 that will follow the contraction of the length of the elongated expandable member 78. The indicator 101 is preferably viewable by a user through the outer housing 74 and indicates the status of the injection device 7 and the progress of the injection. Alternatively, the expandable member 78 is configured with a constant wall thickness and may be pre-stressed during manufacture to bias it to fill from the proximal end 129 to the distal end 128 and collapse or empty in a progressive manner from the distal end 128 to the proximal end 129, as previously discussed.

Referring to fig. 36-39, the elongated expandable member 78 of the injection device 7 may be configured with a section 130 of the expandable member 78 near the proximal outlet end 130 that fills first and collapses last during filling and expulsion of the injection agent 79 from the injection device 7. In other words, during filling of the injection device 7 by the transfer apparatus, it is advantageous to fill the most proximal outlet section 130 of the expandable member 79 first with the injection agent. In addition, during dispensing of the injection agent 79 from the injection device 7, it is advantageous to have the last remaining volume of the injection agent 79 contained within the most proximal outlet section 130 of the expandable member 79. The above configuration has several advantages. The end section 130 of the expandable member 78 may have a thin wall that allows it to remain expanded at a lower pressure than the rest of the expandable member 78. This will ensure that the segments 130 of the expandable member 78 will remain expanded until all of the injection 79 has been expelled from the remainder of the expandable member 78. As previously discussed, the section 130 may be directly coupled to an empty indicator to provide an indication of full or empty. Additionally, as previously discussed, the section 130 may be mechanically coupled to a purge indicator to allow automatic retraction of the button 77 and needle 82 when the injection 79 is fully expelled.

Referring to fig. 36-39, alternatively or in addition to varying the wall thickness 126 of the expandable member 78, an elongated internal mandrel or shaft 124 within the expandable member 78 may progressively (linearly or stepwise) decrease in cross-sectional dimension along the length of the expandable member 78 from a proximal end (outlet end) 129 toward a distal end (closed end) 128 of the expandable member 78. In addition, the manifold 121 allows the expandable member 78 to be attached to the injection device 7, the manifold 121 may also be configured with a large diameter section 130 at the proximal end 129 of the expandable member 78. The large diameter section 130 of the manifold 121 or mandrel 124 at the proximal outlet 129 of the expandable member 78 ensures that the expandable member 78 will first fill with the shot 79 in this area 129. In other words, the expandable member 78 is maintained at a fill diameter almost at the proximal outlet 129 by the mandrel 120 or the large diameter section 130 of the manifold 121. As the fluid 79 first begins to fill the expandable member 78, it first reaches the fill diameter in the large diameter section 130, and then progressively fills along the length of the expandable member 78 from the proximal end 129 to the distal end 128, as previously discussed.

Referring to fig. 36-39, as previously discussed, during dispensing of the injection 79 from the expandable member 78, the diameter of the expandable member 78 at its distal end is continuously collapsed in a gradual manner from its distal end 128 to the proximal end 129 (similar to deflation of a long, tiny balloon) until all fluid is expelled from the expandable member 78. The mandrel 124 or the large diameter section 130 of the manifold 121 at the proximal outlet 129 of the expandable member 78 provides the same benefits during dispensing of the injection 79 (as previously described for filling). The large diameter section 130 ensures that the last remaining fluid 79 in the expandable member 78 will be contained and dispensed from the region 130. As previously discussed, the section 130 may be directly coupled to a purge indicator to provide an indication of full or empty and automatic withdrawal of the button 77 and needle 82 upon completion of the discharge of the injection 79.

Operation and method

Referring to fig. 40-42, the sterile injection device 7 is attached to the transfer apparatus 3 within a covered tray 132, and the individually packaged vial holder 2 with filled vial(s) is provided in a carton 131. The user places the carton 131 on a clean flat surface. The user opens the lid 133 to the carton 131 to expose the transfer device 3 and the vial holder assembly 2. The user removes the cover 132 from the transfer device tray 3 to expose the transfer device 3 and the injection means 7. The user is instructed to leave the transfer apparatus 3 in the carton 131 and to remove only the injection device 7 when alerted.

Referring to fig. 43-44, at the time of use, the user will remove the vial carrier assembly 2 from the carton 131. The user will then remove the vial cap from the vial using the attached cap remover. The user inserts the vial holder 2 into the transfer device 3. The user pushes the vial holder 2 with the attached vial 16 into the transfer device 3 to actuate the system 1. In the illustrated embodiment, this will do three things. First, it locks the vial holder 2 with the attached vial 16 in a lower position within the transfer apparatus 3. It will then automatically initiate fluid communication between the contents 23 of the vial 16 and the transfer device 3 by introducing the access member through the septum of the vial. Third, it will start the mixing (if necessary) and transfer sequence (sequence) of the transfer device 3. This sequence of events will occur automatically and no further input from the user is required to proceed.

Referring to fig. 45-47, in a dual vial system 4 where mixing is desired, the user may have the ability to adjust the delivered dose. The dose selector 48 moves from the initial position shown in figure 46 to the final delivery volume position in figure 47. In this position, the vial holder 5 is freely depressed by the user for allowing mixing and transfer to begin. First, diluent fluid is transferred from a diluent vial and introduced into a powdered lyophilized injection vial. The fluid will be introduced into the powder vial in such a way that when the fluid is transferred from the vial, all of the powder is also removed. The mixing of the diluent and powder may take place entirely in the powder vial or may be accomplished in the transfer device. Static or dynamic mixing elements may be incorporated into the transfer apparatus by the transfer apparatus or introduced into the powder vial to allow for thorough (adequate) mixing of the powder drug or other injectate and diluent. Mixing may be done in a few minutes. Mixing will be performed in as gentle a manner as possible to minimize bubbles/foam and shear stress in the mixture. Mixing will also be done in such a way as to promote complete mixing of the powders and no particles are present. An in-line filter, valve or other device may be employed to remove particulates or air. There may be an indicator on the transfer device showing that mixing is in progress.

Referring to fig. 45-47, in the dual vial system 5, reconstituted solutions are mixed in a powder vial or transfer device 6 and a set volume of solution, either specified by the manufacturer or set by the user, is automatically transferred into the pressurized dosage chamber. The set volume is then automatically transferred to the injection device 7. The tubing, catheter valves and any other volumetric fluid paths between the vial and the transfer device 6 will be minimized to facilitate the transfer of the maximum percentage of the drug to the injection device 7.

Referring to fig. 48-50, once the required dose volume has been delivered to the injection device 7, there are transparent areas or other indicators 80, 101 in the injection device 7 to allow the user to view the mixed solution to verify that mixing is complete. Ideally, the user can observe the entire volume of medicament within the injection device 7. There may also be an indicator 101, such as a relative filling gauge, to show that the correct dose has been delivered to the injection device 7. Completion of mixing and transfer to the injection device 7 will then "unlock" the injection device 7 and allow it to be removed from the transfer apparatus 3, 6 or injection device docking station. The injection device 7 may indicate to the user that it is in a ready state, with the button 77 in an upper or ready position and the indicator windows 80, 101 showing that the injection device is full.

Referring to fig. 50, the user may disconnect the injection means 7 from the transfer device 3 by twisting or pulling the injection means 7 away from the transfer device 3. During removal of the transfer device 7, the adhesive tape pad may be automatically removed, exposing an adhesive surface on the bottom of the injection device that may be used to adhere the device to the patient's skin. Alternatively, the padded strap may have a tab that the user pulls to manually remove prior to adhering the device to the skin.

Referring to fig. 51, the user attaches the injection device 7 to his skin 99. On the bottom of the injection device 7 there may be an adhesive allowing free hand manipulation and attachment to the skin 99 surface. The adhesive may extend past the contour (outline) of the injection device to allow the user to securely attach the band to the skin. Alternatively, the user may hold the injection device 7 against the skin 99 for the duration of the injection.

Referring to fig. 51-53, the user removes the safety device 100 and depresses the button 77 on the injection means 7 to start an injection. Once the button 77 on the injection device 7 is fully depressed it is locked in place and the needle will be fully inserted into the patient and the injection device 7 will begin dispensing the injectate medicament. The injection means 7 may alert the user that a drug injection has started. The warning may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination. The time of injection may range from a few seconds to a few hours. The injection device 7 may be locked in the down position with the button 77 and the indicator window 101 showing that the injection device 7 is not too full to indicate to the user that it is dispensing. The injection device 7 preferably has a transparent section 80 that allows a user to easily determine the amount of medicament remaining in the injection device 7.

Referring to fig. 54, the user will be alerted when the injection of the medicament is complete. The warning may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination. The injection device 7 may indicate to the user that it has completed dispensing by tactile and audible sound that the button 77 is moving to the locked up position and the indicator window 101 shows the injection device empty. At the end of dispensing, the needle will automatically retract to a locked position within the injection device 7.

Referring to fig. 54, upon removal of the injection device 7 from the skin 99, the bandage 120 may be released from the injection device 7 and remain on the skin surface 99. Upon removal from the skin 99, the injection device 7 will preferably be locked, preventing non-destructive entry of a needle or re-use of the injection device 7. The injection device 7 may indicate to the user that a full dose has been delivered. The indication may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination.

According to further aspects of the present subject matter, when administering an injection with a syringe and needle, which means injecting under the skin, it is desirable to know whether the needle is correctly placed in the skin or incorrectly placed in the blood vessel. It is often the case for a user performing an Intradermal (ID), Subcutaneous (SC) or Intramuscular (IM) injection to aspirate the syringe by pulling back on the plunger to create a pressure drop within the syringe to see if any visible blood rises to the needle into the syringe. If blood is observed, this means that the tip of the needle is in the vessel. Large amounts of injectate drugs for subcutaneous injection specifically indicate no injection into the blood vessel. Blood aspiration using a syringe and needle is a common technique and can be performed by anyone with adequate (adequate) training. However, as more drugs are present in automatic injection devices, there is no ability to manually aspirate these types of systems. Once the injection device is placed on the skin and the needle is fired, there is no way for the user to know whether the needle is correctly placed in the skin or incorrectly placed in the blood vessel. Accordingly, there is a need for blood aspiration devices and methods within automatic injection devices.

Referring to fig. 55-56, the injection device 7 may have a needle 85 with a side aperture 108 operably engaged with a button 77 slidable within a septum 109 for advancement into the skin 99. The button 77 may have a viewing window 160 on the button top 103 in fluid communication with the proximal end 161 of the needle 85. The button top 103 may include a cavity 162 for blood 159 to accumulate and be viewed by a user through the button window 160. The cavity 162 may include a central aperture 163 that allows fluid communication with the proximal end 161 of the needle 85 via the needle lumen 165. The outer wall 164 of the cavity 162 is formed by the button top 103. Additionally, a portion of the outer wall 164 may include a hydrophobic filter 166. In this configuration, the proximal end 161 of the needle 85 is at atmospheric pressure. If the fluid 14 or blood 159 travels up the inner lumen 165 of the needle 85, it exits the proximal end 161 of the needle 85 and fills the cavity 162. The air 167 in the cavity 162 is easily displaced through the hydrophobic filter 166 until all of the air 167 has been displaced from the cavity 162 and it is filled with fluid 14 or blood 159. At this point, the flow of fluid 14 or blood 159 ceases because fluid 14 or blood 159 cannot penetrate hydrophobic filter 166 and can be easily viewed by the user through window 160 of button top 103, thus providing a means for determining whether needle 85 of injection device 7 is in blood vessel 158.

Referring to FIG. 57, insertion of the needle into tissue can be generally divided into four stages. These stages include touchless, boundary displacement, tip insertion, and shaft insertion. During boundary displacement, the tissue boundary in the contact region deflects under the influence of the load applied by the needle tip, but the needle tip does not penetrate the tissue. As the needle tip begins to penetrate the skin, the boundary of the skin reaches a point of maximum boundary displacement in the contact area along the tip of the needle. After the needle tip penetrates the skin, the shaft is inserted into the tissue. Even after insertion of the tip and shaft, the boundary of the skin surface in the contact area does not return to its initial non-contact state but remains displaced by a distance x. The amount of boundary displacement x is a function of several parameters including, but not limited to: needle diameter, needle tip geometry, needle shaft friction, needle insertion speed, and physical skin properties. The boundary displacement x of the skin in the contact area is characterized by a needle-based injection device, since it affects how much the needle penetrates the skin and thus reduces the actual needle penetration depth by the amount of the boundary displacement x. If the boundary displacement x can be intentionally induced by stretching or preloading (such as pushing the skin out at the contact site prior to needle tip insertion), there will be no additional boundary displacement through the needle tip or shaft during insertion and the needle tip depth can be predictably defined. An advantage of this intentional displacement is that the amount of needle penetration into the tissue will not be affected by the variation of the boundary displacement x. Without intentionally causing boundary displacement at the skin surface prior to needle tip insertion, the actual depth of penetration of the needle into the skin is not specifically known, since some needle length (according to the aforementioned parameters) is outside the skin due to the naturally occurring boundary displacement x shown in fig. 57. On the other hand, if the maximum boundary displacement can be caused at the contact site, the actual needle penetration depth will not vary with the above parameters including needle diameter, needle tip geometry, needle shaft friction, needle insertion speed and physical skin properties.

Referring to fig. 58, the injection device 7 may have a skin boundary displacement extension or structure, such as the lower side surface 76, that includes an extension 138 at or around the dispensing port 82 or as part of the dispensing port 82. The extension extends substantially perpendicular to the tissue plane at the needle insertion point. When the injection device 7 is attached to the skin 99, the extension 138 will protrude against the skin 99 surface, causing the skin 99 to be displaced or compressed in this contact area 139. The compression of the skin helps to reduce or eliminate "tenting" of the tissue surface upon needle insertion. In other words, extension 138 serves to eliminate further tissue deformation or tenting, or to cause a more reproducible and lesser amount of skin surface deflection or tenting, by compressing the tissue to "preload" it. During actuation of the button 77 from the pre-firing state to the first position, the needle 85 protrudes from the injection device 7 through the dispensing opening 82 and/or the extension 138 into the skin 99 to start dispensing the medicament. For the reasons described above, as the needle 85 is extended from the injection device 7, the tip of the needle 107 does not generate an additional boundary displacement 141 (already deliberately induced by the extension 138) in the skin 99 of the contact area 139. Thus, the depth 140 of the actual needle penetration into the skin 99 is better characterized and controlled. Moreover, the extension through which the needle passes immediately compresses the tissue surrounding the needle, which has several advantages. During injection, compression of the tissue by the extension 138 in the contact region 139 increases the local density of the tissue, thus creating a higher pressure region compared to the surrounding adjacent tissue 99. When the injectate enters the skin 99, fluid will migrate from this high pressure zone 139 to a low pressure area in the skin 99, which helps prevent the injected fluid or drug from flowing or migrating into the immediate area near the needle/skin puncture site, and serves to reduce or minimize fluid leakage (reflux) and/or prevent bleeding at the puncture site. The high pressure zone also effectively provides the benefits of a longer needle. Experimental data confirm this. In the ultrasound evaluation, the subcutaneous deposition depth of a 10mL bolus of liquid (saline) using an injection device 7 with a needle depth of 5mm was compared with an off-the-shelf infusion pump (free 60, RMS) with a butterfly needle extension set (needle depth of 9mm), and the results showed that the subcutaneous depth of the 10mL bolus after injection corresponded to between an injection device 7 with a needle length of 5mm and a pump with a needle length of 9 mm. In all results, the bolus location was characterized by the distance from the skin surface to the top edge of the bolus (Zd). FIG. 103 shows the top edge of a 10mL subcutaneous bolus using a 9mm needle length pump. The distance Zd was 0.44 cm. Fig. 104 shows the top edge of a 10mL subcutaneous bolus using an injection device 7 with a 5mm needle length. The distance Zd was 0.42 cm. Thus, a similar bolus depth has a needle depth (5mm) and the tissue displacement structure is more than 40% shorter than another test needle (9mm) without tissue displacement structure.

Another advantage of the extension 138 is to compress the tissue in the contact region 139 after injection is complete. In the post-fired state, the button 77 pops up, alerting the user that the injection device 7 has been completed. The needle 85 is completely withdrawn from the puncture hole in the skin 99. The dwell time between the completion of dispensing of the injection device 7 and removal by the user may be a few minutes or more depending on the environment in which the user is located at the time of completion. For the same reasons as previously described, the compression of the tissue by the extensions 138 in the contact region 139 increases the local density of the tissue, thus creating a higher pressure zone than the surrounding adjacent tissue 99. This pressure helps close the puncture and prevents backflow of injected fluid or medication to the injection site, and acts to reduce or minimize leakage and/or bleeding of fluid from the puncture site, similar to the way a nurse applies pressure to the injection site with the thumb after injection.

Referring to fig. 60, the vial access member 21 of the transfer device 3 may include a plurality of lumens, such as a multi-lumen tube 34, to communicate with the internal fluid channel 35 of the transfer device 3. Vial access member 21 preferably includes an inlet tube 36 that allows air or fluid to enter vial 12 and an outlet tube 37 that allows air or fluid to exit vial 12. Lumen opening 38 in vial access member 21 may be oriented such that inlet tube opening 36 is above outlet tube opening 37 when the vial is inverted and attached, such as illustrated in fig. 59. This orientation allows air or liquid to be introduced through the upper inlet tube 36 and vial contents 14 to be output through the lower outlet tube 37. Also, the outlet opening 37 may be positioned near the bottom of the lower end of the inverted vial 12, near the septum 19 to facilitate the entire contents 14 of the vial 12 entering the outlet 37 and being removed from the vial 12. Once the vial 12 is mounted in the vial holder docking area 29 in the transfer device 3, the vial access member 21 is able to access the contents 14 of the vial 12. When the transfer device 3 begins to withdraw the contents 14 from the vial 12 through the outlet tube 37, a pressure drop 154 occurs in the vial 12. This pressure drop 154 causes displaced air 58 to be drawn into the vial 12 through the inlet opening 37 of the vial entry member 21 to replace the fluid 14 being drawn. In some instances depending on the amount of injection 14 in vial 12, liquid level 153 in vial 12 may be above vial entry member 21 and particularly above inlet tube opening 37. As air 58 is drawn into vial 12 through inlet opening 37, it creates bubbles 155 in fluid 14. The buoyancy forces cause the air bubbles 155 to migrate to the top of the vial 12 along with the air 58 present. In some injectables 14, it is undesirable to introduce air bubbles 155 into the solution. This causes more bubbling, foaming, and/or frothing within the fluid 14.

Referring to fig. 61, the extension member 156 may be slidably movable within the inlet opening 36 of the vial access member 21. The outer diameter of the extension member 156 may closely match the inner diameter of the inlet opening 36. The extension member 156 may have an inner diameter that allows air 58 to pass therethrough. As air 58 is drawn into vial 12 through inlet discharge opening 36 due to pressure drop 154 in vial 12, air 58 first pushes piston-like extension member 156 into inlet opening 36. The extension member 156 is long enough not to exit the inlet opening 36. The extension member 156 continues to slide through the inlet opening 36 until the end of the extension member 156 stops at the top 157 of the vial 12, just above the liquid level 153 in the vial. The top of the inverted vial 12 acts as a stop for the extension member 156. The tip of the extension member 156 may be tapered so as not to block flow through the inner diameter of the inverted vial 12 when in contact with the top thereof. Air 58 continues to travel through the inner diameter of extension member 156 until all of the fluid 14 in vial 12 has been withdrawn from vial 12 through outlet tube 37. As previously mentioned, the outer diameter of the extension member 156 is a close fit with the inner diameter of the inlet opening 36 so as not to allow air to leak between its interfaces. The extension member 156 ensures that no air 58 is introduced into the liquid 14 within the vial 12, causing an air bubble 155.

Referring to fig. 62, pressure chamber 59 may be configured with an inlet 168 for bringing fluid 14 and air 58 into the chamber. Additionally, the pressure chamber 59 may be configured with an outlet 64 for discharging the fluid 14 and/or air 58 out of the chamber 59. These holes 168, 64 may be positioned off-center of pressure chamber 59 to help control the order in which liquid 14 and air 58 are introduced into pressure chamber 59 and/or discharged from pressure chamber 59. As previously mentioned, the outlet 64 of the pressure chamber 59 may be oriented below the inlet, with all of the liquid 14 being expelled first, then the remaining air 58 being expelled, and finally any air in the chamber 59 will be directed to the top of the pressure chamber 59 during the process of expelling the liquid 14 from the pressure chamber 59. Additionally, as shown in fig. 62, the outlet profile 169 may be configured in a non-circular shape to further facilitate the entire liquid content 14 of the pressure chamber 59 to enter the outlet 64 and be removed from the pressure chamber 59 before the air 58 is removed from the pressure chamber 59. Additionally, as shown in fig. 62, a portion 170 of the outlet 64 may be positioned below a surface 171 of the pressure chamber 59. This may act as a trap to further encourage the entire liquid content 14 of the pressure chamber 59 to enter the outlet 64 and be removed from the pressure chamber 59 before air is removed from the pressure chamber 59.

Referring to fig. 63, when liquid 14 is removed from vial 12 using vial access member 21, only fluid 14 passing through outlet opening 37 is removed until liquid level 153 drops to the top of outlet opening 137. At this point, the mixture of liquid 14 and air 58 will be removed. The vial access member 21 may additionally have an outlet opening 37 configured in a non-circular shape with reference to fig. 63 such that the opening height is reduced and the opening width is increased to further allow more liquid content 14 of the vial 12 to enter the outlet 37 and be removed from the vial 12 before the air 58 is removed from the vial 12.

Referring to fig. 64 and 65, the combination of a hydrophobic filter 68 and a hydrophilic filter 69 in the fluid channel 35 between the vial 15 and the injection device 7 may preferably allow filtration of the drug 14 and removal of air 58 during the transfer process. These filters may be separate components or combined into one component. Each filter may be constructed of different materials including, but not limited to, Mixed Cellulose Ester (MCE), polyvinylidene fluoride (PVDF), Polytetrafluoroethylene (PTFE), nylon, and Polyethersulfone (PES). Each filter may have a pore size in the range of 0.22 to 3 microns. Each filter may have a coating that makes it hydrophilic or hydrophobic.

When an injection intended to be injected under the skin is administered, a common response is swelling of the injection site. This reaction is particularly prominent in a single subcutaneous site where the injection volume is high and/or the injection rate is fast. When these injections are administered using a syringe and needle or administration set, the injection site swelling is not a result of the injection device. However, as more drugs are present in an automatic injection device that is attached and worn on the body during infusion, site swelling poses a challenge to keeping the automatic injection device secured to the body. In particular, if the adhesive on the injection device is improperly designed, bumps or bumps formed by the injected solution at the skin surface may dislodge (disridge) the automatic injection device from the injection site. Accordingly, there is a need for an automatic injection device with a correctly designed adhesive that allows bulging at the injection site without compromising the attachment of the device to the patient.

Referring to fig. 66, there are two interfaces involved in adhering the injection device 7 to the skin 99. The first interface is an adhesive/device interface 173 and the second interface is an adhesive/skin interface 174.

Referring to fig. 67, the adhesive 88 may be disposed on the injection device 7 using at least two regions. The first region 175 may comprise a permanent bond using mechanical or chemical means between the adhesive 88 and the injection device 7 and is preferably positioned within the perimeter of the injection device 7. The second region 176 may be configured to be detachable or detachable from the injection device 7 and preferably adjacent to the outside of region 1 (e.g. radially outwards) and outside of region 1.

Referring to fig. 68, if the adhesive 88 is fully attached to the bottom 76 of the device 7, during the tissue bulge 177 event, the adhesive 88 at the adhesive/skin interface 174 will begin to peel away from the skin 99 because the interface 174 is weaker than the adhesive/device interface 173. This is shown on the bulged surface in fig. 68. This may cause the injection device 7 to be dislodged from the skin surface 99 and fall away from the patient.

Referring to fig. 67 and 69, instead of completely permanently attaching the adhesive 88 to the bottom 76 of the injection device 7, as shown in fig. 68, the adhesive 88 may be provided on the injection device 7 with the above-described regions 175, 176. During the tissue bulge event 177 in this configuration, the adhesive 88 in the area 176 in both regions will detach from the injection device 7 and securely attach to the skin surface 99 at the adhesive/skin interface 174. This will allow the peel edge 178 to transfer from the adhesive skin interface 174 to the adhesive/device interface 173, effectively creating a stress relief at the adhesive/skin interface. The adhesive/device interface 173 may be designed to be stronger and prevent the injection device 7 from detaching from the skin surface 99.

When performing self-injection with an automatic injection device, it is a beneficial need for the device to protect the user from accidental needle sticks. Typically, the needle is retracted into the device before and after use, preventing the user from accessing the needle. However, during injection, the needle extends outside the device. If the automatic injection device is worn and inadvertently falls off the user during injection, the needle will be exposed, creating a possible needle stick hazard to the user. Therefore, there is a need for an automatic injection device with a skin dislodgment sensor that automatically retracts the needle if the device is dislodged from the skin during injection.

Referring to fig. 70-72, skin dislodgment sensor 179 may be operably engaged with flexible latch 181 of button 77 and slidable within lower housing 180 of injection device 7. Referring to fig. 71, when the injection device 7 is attached to the skin surface 99, the skin dislodgment sensor 179 is forced into a first or upper position 182 within the injection device 7. When button 77 is actuated to the firing state or second or dispensing position (exposing needle 85), flexible latch 181 is forced into a locked position 187 by skin expulsion sensor 179 below latch plate 183. Latch plate 183 holds button 77 down at latch plate surface 184 on button 77 in the fired state or dispensing position until dispensing is complete. At the end of dispensing, the latch plate 183 translates away from the latch plate surface 184 on the button 77, allowing the button 77 and needle 85 to retract to a post-firing position in which the needle 85 is contained within the injection device 7. Referring to fig. 72, in case the injection device 7 is dislodged from the skin surface 99 during injection, the skin dislodgment sensor 179 extends to a second or lower position 185 outside the injection device 7. This allows the flexible latch 181 to spring back to the unlocked position and disengage from the latch plate 183. This allows the button 77 and needle 85 to be retracted to a post-firing position in which the needle 85 is contained within the injection device 7.

When performing self-injection with a syringe and needle, the user may have a need to temporarily stop or pause the injection due to severe pain or irritation at the injection site. This pause in the flow of the injection into the injection site, with the pressure on the plunger rod of the syringe removed, helps to reduce pain at the injection site by allowing the injection fluid bolus more time to diffuse into the surrounding tissue and thus reducing local pressure and associated pain and irritation. However, as more medication is present in an automatic injection device, there is no ability to manually pause these types of automatic systems. Once the automatic injection device is placed on the skin and the cannula is introduced, the user has no way to pause the injection due to pain or irritation at the injection site. Accordingly, there is a need for a user to be able to pause an automatic injection system.

Referring to fig. 73-74, upon actuation of the button 77, the needle 85 and the button 77 travel to a first position or depth, as shown in fig. 73. In this first position or depth, the side hole 108 is covered by the septum 109 and thus the internal lumen 165 of the needle 85 is not in communication with the fluid passageway 86 of the dispensing port 82. The button 77 may be intentionally held in this first position or depth to prevent the flow of the injection 14 from the fluid passageway 86 into the side aperture 108 of the needle 85 and into the skin 99. As shown in fig. 74, when the button 77 is released, the needle 85 and button 77 return to a second or dispensing position in which the side aperture 108 is exposed to the fluid passageway 86, allowing flow of the injection agent 14 from the fluid passageway 86 into the side aperture 108 of the needle 85 and into the skin 99 until the injection is complete. This action of pushing the button 77 to the first position or depth can be performed as many times as desired throughout the injection.

Referring to fig. 75-76, the actuation force 186 of the button 77 is the transitional load applied to the button 77 required to begin displacing the button 77 and needle 85 from the pre-firing position to the firing state or dispensing position. Until this transitional load is met, the force 186 applied to the button 77 is transferred directly to the injection device 7. In particular, this load 186 may be transferred to the adhesive skin interface 174 and/or the adhesive means interface 173 resulting in a better fixation of the injection means 7 to the skin surface 99 before activating the injection means 7.

Referring to fig. 77, an indicator window 172 on the transfer device 3 may be provided to show that the transfer and/or mixing of the fluid 14 is proceeding. The indicator window 172 may be disposed in the base of the transfer apparatus 3 and track the movement of the plunger 93 of the pressure chamber 56 within the transfer device 3. Indicator window 172 may be configured with a scale or other means to track the movement of plunger 93. Alternatively, the plunger 93 may be configured with a different color to make it easy to track its movement in the indicator window 172. The combination of indicator window 172 and plunger 93 may provide for the progress of the withdrawal of fluid 14 from vial 12 and the filling of chamber 56. The combination of the indicator window 172 and the plunger 93 may also provide for the progress of the transfer of fluid 14 from the chamber 56 to the injection device 7.

Referring to fig. 78-79, the arcuate expandable member 78 is positioned and/or will preferably expand in length in an arcuate shape. In the illustrated embodiment, the arcuate shape is caused by providing a less elastic region (e.g., a thicker or relatively thick wall thickness region 126) that will result in less deflection of the expandable member in that region and result in the formation of an expanded arcuate shape. The thick wall thickness region 126 may be configured in any shape that will allow for an arcuate shape in the expandable member 78 during expansion. The preferred configuration of the thick wall thickness region 126 is to minimize its thickness or attachment 150 in the circumferential direction on the expandable member 78 and maximize the radial thickness or protrusion 151 away from the expandable member 78. This serves to encourage the expandable member 78 to expand in an arcuate shape but also to maximize the amount of material along the contour unaffected by the thick wall thickness area 126 used for expansion. Additional features including, but not limited to, a T-shape may be provided to the end of the radial protrusion 152 to help urge the expandable member into the arcuate shape.

Referring to fig. 80, the volume of the pressure chamber 56 may be set to be greater than the total fluid volume 14 in the vial 15 such that additional air 58 is drawn from the vial 15 into the chamber 56. This additional air 58 may help ensure that all of the liquid 14 is removed from the vial 15 and that residual liquid 14 is removed or purged from the fluid passageway 35 between the vial 15 and the chamber 56. Additionally, during transfer of the liquid 14 from the chamber 56 to the injection device 7, additional air may facilitate removal or purging of residual liquid 14 in the fluid channel 35 between the chamber 56 and the injection device 7.

Referring to fig. 81, the transfer device 3 includes a vial holder docking area 29, which may include an elongated vial access member or piercing member 21. The vial holder docking area 29 may include a vial access protector 136. The vial access protector 136 is locked and held in a first position over the vial access member 21 by locking fingers 137 in the vial holder docking area 29 prior to insertion of the vial 12 or vial holder to cover the vial access member 21 and prevent accidental vial access member puncture by a user. When the vial 12 or vial holder is inserted into the vial holder interface area 29, the vial 12 or vial holder displaces the locking fingers 137 and unlocks the vial entry protector 136. Once unlocked, the vial access protector 136 is movably slidable with the vial 12 or vial holder within the vial holder docking area 29.

Referring to fig. 82, a flow restrictor 55 may be used in the fluid passage 35 to control and/or delay the transition time and/or increase the mixing time. Small lumen tubing may be used at any point in the flow path 35 to restrict flow and increase mixing/transfer time multiple times for an hour or more. A way to control and/or delay the transfer time and/or increase the mixing time between the second pressure chamber 42 and the injection device 7 is to use a multi-lumen fluid channel 142 between the second pressure chamber 42 and the injection device 7. Each lumen 143, 144 of fluid passage 142 is attached to a specific location 145, 146 on second pressure chamber 42, preferably spaced apart along the travel of the piston and having an inner diameter 147, 148, the inner diameter 147, 148 being sized so as to provide a specific flow rate through the lumen 143, 144 based on the pressure within second pressure chamber 42. Initially, as the second pressure chamber piston 46 begins its advancement in the chamber 42, the fluid mixture 14 is dispensed through all of the lumens 143, 144 in the fluid passage 142 to the injection device 7. Once the piston passes over the attachment point 145 between the lumen 143 and the pressure chamber 42, the flow of fluid through that lumen 143 ceases and the fluid 14 is forced through the remaining lumens 144. The multi-lumen tube and the attachment point may be located along the pressure chamber. The size of the last lumen 144 available from the flow of fluid 14 may be such that it has a very small inner diameter 148. Thus, the flow rate will be very low, increasing the time for transfer of the fluid 14 from the chamber 42 to the injection device 7. The delay of this transfer allows the mixing time to increase.

Referring to fig. 83, a safety device, such as a safety pin or safety sleeve 100, may be configured to allow removal from the injection device 7 in any direction to release the injection device 7 ready for firing (injection).

Referring to fig. 84, the injection device 7 comprises a needle 85 with a side hole 108 allowing fluid communication between the fluid pathway 86 and the skin 99 once the button 77 is sufficiently depressed in the injection device 7. This begins the dispensing of injectate 14. The inner diameter 165 of the needle 85 is important in controlling the rate of dispensing from the injection device 7. Referring to the Hagen-Poiseuille equation for fluids flowing in a pipe, the flow rate through a pipe is proportional to the radius of the pipe multiplied by the fourth power. Thus, a small change in the inner diameter 165 of the needle 85 results in a large change in the flow through the needle 85, particularly as the inner diameter 165 becomes smaller. The needle 85 in the injection device 7 may vary from 21G to 34G (stubsironwiregaugesystem) in various wall thickness configurations. This range corresponds to an inner diameter 165 range of 0.021 "to 0.003", recognizing that there are manufacturing variations or tolerances in the needle inner diameter 165 in any given needle size. This is based on the needle size and may have as much variation in inner diameter as ± 0.00075 ". To limit the variation in the range and flow rate of the inner diameter 165 within any given needle size, the needle 85 may be modified prior to assembly to the injection device 7. The modification may include crimping, flattening, or rolling the needle from a circular shape to a non-circular shape over a portion of the length of the needle 85 to a new prescribed effective inner diameter 165. This has the advantage of allowing control of a particular delivery rate from the injection device 7.

Referring to fig. 85-86, the lumen opening 38 in the vial access member 21 may be oriented to allow pressurized air or liquid to be introduced through the upper inlet tube 36 and to allow the vial contents 14 to be output through the lower output tube 37. Also, the outlet opening 37 may be positioned adjacent the inverted vial 12, adjacent the septum 19 to facilitate entry of the entire contents 14 of the vial 12 into the outlet 37 and removal from the vial 12. The preferred sequence for removing the contents 14 from the vial 12 is first all of the fluid 14 in the vial 12 and then air 58 from the vial 12. This is achieved with the current embodiment when the orientation of the transfer device 3 is as shown in fig. 85-86. This sequence of all fluid 23 and then air 58 removal is achieved until the angle of the transfer apparatus to the horizontal is +/-45 degrees based on the geometry of the vial access member 21 within the vial 12. Beyond this angle, there is a possibility that air 58 may be introduced before or during removal of fluid 14 from vial 12. The angle sensor 149 may be positioned in the vial access member 21 or around the vial access member 21 to sense the angle of the transfer device 3. It may be in direct communication with either or both of the lumen openings 38 and/or each or both of the inlet and outlet tubes 37, 36. In the current embodiment shown in fig. 85, the sensor 149 allows fluid communication between the outlet 37 and the fluid channel 35 when the diversion apparatus 3 is at an angle of less than 45 degrees. As shown in fig. 86, if the transfer device 3 is tilted to an angle greater than 45 degrees, the sensor 149 may be rotated or translated to a new position to shut off fluid communication between the outlet 37 and the fluid channel 35.

Referring to fig. 87, an alternative transfer apparatus 3 is provided within a single vial system that does not perform mixing but rather transfers only fluid 14 from a single vial 12 to an injection device 7. The alternative transfer device 3 comprises a vial 12, a variable volume pressure chamber 56 and a fluid channel 35 to guide the contents 14 from the vial 12 into the injection means 7. Inlet tube 36 of vial access member 21 is connected to variable volume pressure chamber 56 with fluid passage 35. The outlet tube 37 of the vial access member 21 is connected to the injection device 7 by a fluid passage pressure chamber 56.

Referring to fig. 87, full insertion of the vial 12 by the user into the transfer device 3 causes the vial access member 21 to be introduced through the septum 19 of the vial 12 to access the contents 14 of the vial 12. This also triggers the release of the pressure chamber trigger 59. The plunger 60 is in the retracted position and the pressure chamber 56 is filled with air 135. Pressure release trigger 59 releases plunger 60 within pressure chamber 56 which is connected to dispensing spring 63. Dispensing spring 63 advances plunger 60 and displaces air 135 from pressure chamber 56 through inlet tube 36 into individual vials 12. Air 135 entering vial 12 displaces fluid 14 from vial 12 through outlet tube 37 into injection device 7. This continues until all of the fluid 14 is displaced from the vial 12 into the injection device 7. Check valve 40 may be used to prevent fluid 14 from passing back into vial 12 or to prevent fluid 14 from passing back into pressure chamber 56.

Syringe content transfer

The present subject matter is directed in part to a single-use, single-use apparatus and method for transferring, upon user activation, the injection contents of one or more standard syringes, preferably into an injection device and, preferably, simultaneously pressurizing the injection device for subsequent automatic injection into a subject. The apparatus and methods described herein may have any suitable detailed configuration, but are preferably configured to transfer the contents of a syringe into an injection device. The apparatus and method may use any of the features or aspects described above, alone or in combination with features or aspects described below and/or shown in the drawings. Furthermore, the apparatus may be configured to allow a user to select a dose volume to be transferred to the injection device and subsequently delivered to the subject. The apparatus may further be configured to filter the contents to remove particles or drug particles prior to transfer into the injection device, and may include a sterile filter for filtering any displaced air trapped in the one or more syringes. The device may further be configured with a one-way valve to only allow the user to transfer the injectant from the syringe into the injection device. Also, the apparatus may be further configured with a one-way valve to prevent backflow of the pressurized injectant in the injection device into the apparatus at the fill port. The device may further comprise locking means to prevent a user from removing the injection means prior to transfer of the medicament or to prevent activation of the injection means until the means has been removed from the transfer means.

In use, a user inserts a filled syringe into the syringe receiving area. The user depresses the syringe plunger or piston to manually transfer the injectant through the transfer device into the injection device. This simultaneously charges the injection device (e.g., by introducing an injection agent under pressure into it to inflate and pressurize the inflatable member or balloon) so that the injection device is ready for automatic injection into the subject upon activation by the user.

Referring to fig. 88-90, a single use disposable manual injector transfer and injection system 189 may include a transfer device 190 and an injection apparatus 7. Referring to fig. 88, the transfer apparatus 190 has, among other features, an outer housing or base 191 made of a rigid molded plastic or other suitable material and defines a syringe docking area or first receiving station 192 for receiving a syringe, such as a standard syringe, and an injection device docking station or second receiving station 193 (for a removable injection device, such as the one described in detail above). In the illustrated construction, the syringe docking station 192 (which may be in the form of a cylindrical recess) and the injection device docking station 193 are spaced apart, such as at opposite ends of the transfer apparatus housing 191. As with the previous embodiment and with the same benefits, the diversion device 190 may have an outer housing 191 integrated into the packaging 194 of the system.

Referring to fig. 89-90, the transfer device 190 has at least one fluid channel 195 extending from a syringe connector port at one end 218, such as a female luer syringe connector within a cylindrical recess, and a port or outlet 219 at the other end, such as in an injection device docking station, for mating or connecting to an inlet of an injection device. The fluid channel 195 may be a single channel or include an array of internal fluid channels 195, as desired, to perform any transfer of the injection agent 196 and to carry or transfer it from the syringe 197 in the syringe docking area 192 to the injection device 7 in the injection device docking station 193. The fluid channel 195 may include a flexible or rigid conduit or tubing 198 forming all or a portion of the channel. The fluid passage 195 may also include a check valve, such as a check ball 199, to control fluid flow from the syringe to the injection device and prevent back flow; one or more filters 200, such as sub-micron filter membranes, to filter the injectate 196 during transfer to the injection device 7. The filter 200 may also have other characteristics, such as hydrophilicity to block air flow to the injection device 7, or hydrophobicity to connect the flow path to the discharge channel and prevent fluid flow through the discharge channel, a restrictor or other means to transport, control and/or direct the drug 196 from the syringe 197 through the transfer device 190 into the injection device 7.

Heating of injection

A large proportion of injectable biopharmaceutical drugs require refrigeration conditions (typically 2-8 ℃) to maintain long-term stability. These drugs must be kept at this lower temperature until use, otherwise treatment failure due to insufficient efficacy occurs. Currently, in use, the patient is required to remove the drug from the refrigerator prior to administration and allow it to warm naturally to ambient or room temperature, which may typically range from about 15 to about 32 ℃. Depending on the drug container, e.g. a packaged or unpackaged vial or a pre-filled syringe, this process may take up to half an hour or more. There are a number of potential problems if the drug/device is not allowed to warm up. First, due to the cold solution temperature, the drug viscosity may increase by a factor of three or more, making it more difficult to inject fluid into a patient through a small needle. Second, if the device is electronically powered, the energy of the cold battery may be greatly reduced and may not be as effective as desired. Third, cold drugs are significantly more painful for the patient being injected. Moreover, due to concerns about child safety, users or patients may be uncomfortable, fear that they may forget it and/or want to conduct their business, not allow their injection device to stay outdoors for long periods of time and open to warm up, when they do not want to wait 30 minutes or more away from home at all.

Many devices for actively heating refrigerated drug/device combinations are currently on the market. Actively heating the drug solution using a heater (e.g., an electric heater) or other technique (at temperatures above room temperature) may increase the cost of the product and may result in overheating and subsequent degradation of the drug, which represents additional expense and complexity for the user. Therefore, for the reasons set forth above, a passive system and method for rapidly, reliably and safely warming a cold or frozen injectate would be highly beneficial to enable a user to conveniently use it quickly and conveniently outside the refrigerator.

In accordance with other aspects of the present subject matter, with reference to fig. 91 and 92, as well as other figures, passive heat transfer may be from the room temperature transfer device 203 and injection device 206 structure and from the environment 201 (including the cold injectate 202 from the room or ambient temperature gas) for illustrative purposes only. Heat transfer may occur, for example, in the transfer device 203 (or other transfer/injection devices described herein) within a fluid channel (generally designated 204) between the vial 205 or syringe and the injection device 206, by contact with a room or ambient temperature gas, and within the injection device. The fluid channel 204 may comprise a tube, conduit, filter, check valve, or other component capable of carrying a fluid, and more particularly, may optionally be made of or in direct electrically conductive contact with a material having a high thermal conductivity.

Such high thermal conductivity materials may be metals such as copper, stainless steel, aluminum or other metals or non-metallic materials having high thermal conductivity that are compatible with temporary contact with a particular fluid. The fluid channels may also be configured to enhance or maximize heat transfer contact between the fluid and the flow path. This may be achieved by maximizing or enlarging the surface of the flow path in contact with the fluid, more particularly, the ratio of flow path surface area to fluid unit volume, such as by increasing the length or decreasing the cross-sectional area of the flow path. Also, the fluid channels may be configured to enhance heat transfer by providing flow paths having or in contact with relatively large high thermal conductivity masses.

In particular, as one non-limiting example, the total mass of the materials (e.g., high thermal conductivity materials) making up and/or in direct thermal contact with the flow path may be substantially equal to or greater than the total mass of the fluid being transferred in order to provide a fast and sufficient heat transfer rate and capacity.

The quality of the thermally conductive flow path or contact material is not the only factor that can be considered in raising the temperature of the drug during transfer. For example, as described above, the fluid flow path may be configured such that the ratio of the surface area in contact with the fluid to the unit volume of the fluid is sufficiently large to achieve all or part of the desired heat transfer. Such flow paths may be configured to provide substantial heat transfer even if non-metallic flow path materials are used, although high heat transfer materials such as metals or materials having heat transfer rates comparable to metals may provide greater or faster heat transfer. Separately or in addition, the flow path may be configured such that work is done (or energy is consumed) on the drug or other fluid in the flow path, which would result in additional heating of the fluid. This is still considered passive heating because no electrical heating source is required, nor is it required to use temperatures above ambient room temperature for heating. For example, a relatively long flow path having a very small cross-sectional dimension or diameter will provide a relatively large surface area and enhance conduction between the surface of the flow path and the drug or other fluid flowing therein. Such systems may also tend to increase the frictional or shear forces exerted on the fluid, which will serve to increase the temperature of the fluid. In order for the liquid to flow through such an elongated small diameter flow path at a sufficient flow rate, significant pressurization of the fluid may also be required, such as by a mechanical pump or pneumatic pressurization, which also tends to raise the temperature of the fluid. These various features (flow path material, mass of fluid flow path and contact material, fluid flow path surface area, and energy dissipated in the fluid during flow through the flow path) may be used alone or in different combinations to achieve the desired heat transfer.

In addition, another additional feature that can aid in heat transfer and increase the temperature of the frozen drug is the use of a gas near room or ambient temperature to effect fluid transfer and flow. In other words, the use of a gas at room temperature or higher to force a drug or other fluid through a flow path may also contribute to heat transfer and temperature rise. More specifically, injecting a near-room temperature gas into a drug vial to force the drug out of the vial will result in a certain amount of heat being transferred from the gas to the liquid drug. Heat transfer from the room temperature gas to the fluid will be further enhanced if the gas also bubbles or otherwise passes through the vial contents. The injection of gas from the variable volume pressure chamber into the vial to force fluid out of the vial was previously described with reference to fig. 9 and 10. The use of a pre-filled pressurized gas cylinder as a motive force to propel injectate through a transfer system is also described in U.S. provisional patent application serial No. 62/138762 filed 3/26/2015, which is incorporated herein by reference in its entirety. As described in any of the examples or embodiments above, the drug transfer and injection systems of the present invention may use one or more of these heat transfer features, alone or in combination, to increase the temperature of the frozen drug.

For example, ambient or room temperature is typically about 15-32 ℃, e.g., about 18-22 ℃ or about 20 ℃. Referring to fig. 92-93, in an ambient temperature passive transfer device 203, a selected volume (typically about 2-8 c or about 4-5 c) of refrigerated injectate 202 can be transferred from a vial 205 or syringe through a fluid channel 204 and heat exchange elements and structures 207 within the transfer device 203 to an injection device 206 at a transfer time of from about 0.05 to up to 3 minutes or more. During this time, the refrigerated injectate solution or other fluid 202 can absorb sufficient thermal energy from the ambient temperature fluid channel 204, from the ambient temperature gas driving the fluid (if used), and from the ambient temperature heat exchange element 207 in the transfer device 203, and from the ambient temperature injection device 206 to reach a temperature within about 5 ℃ or less of ambient or room temperature. The temperature increase may be in the range of at least 5-15 deg.C, such as at least about 10-15 deg.C. For example, a temperature increase of from about 4.5 ℃ to about 13-18 ℃ or about 16-18 ℃ may be achieved in about 80 seconds or less, such as about 30-60 seconds. This assumes that the injectate 202 can be water-based, such as saline-based or distilled water-based, although some light oils can be used with other drugs. The amount of such an injection 202 for a single dose may be up to about 50cc according to the present subject matter. Generally, a single dose may range between about 2cc and 50cc and may be less than about 5cc, depending on the injection and the physician prescription. The viscosity of the injection may vary with the type of injection and the temperature. For example, an injection may have a viscosity of up to about 100 cP.

Referring to fig. 92-93, heat exchange between the ambient environment 201 and the cold injectate medication, solution, or other fluid 202 in the transfer device 203 can occur in a variety of ways. For example, thermal energy may be transferred from the transfer device 203 to the frozen injection fluid 202 by direct conduction within the fluid channel 204 between the surface of the channel and the fluid. The fluid channel 204 can be configured to have a relatively small diameter and/or an extended or longer length to enlarge or maximize the amount of room temperature material surface area of the transfer and/or injection device that is in contact with the cold fluid or solution 202. By way of example only, the fluid flow passage 204 may have an overall length of about 0.5 inch to about 5 inches (1.7-12.7cm), an inner diameter of about 0.01 to 0.1 inch (0.25-2.54mm), and optionally an inner diameter of 0.01-0.05 inch (0.25-1.2mm), preferably about 0.05 inch (1.2 mm). This range of flow path diameters (or equal cross-sectional areas if the flow channel is not circular) applies to all embodiments described above. As previously discussed, the longer flow path length and smaller inner diameter (or cross-sectional dimension) provide a greater surface area for heat transfer from the ambient to the fluid flowing through the channel. The equivalent cross-sectional area of the non-circular flow path is substantially as follows:

circular ID	Equivalent area
		0.1 inch	0.00785 square inches
2.54mm	5.064 square millimeter
		0.05 inch	0.00196 square inch
1.27 mm	1.266 square millimeter
		0.01 inch	0.0000785 square inches
0.254 mm	0.0506 square millimeter

Thermal energy may also be transferred to the cold fluid 202 by convection from the introduction of room temperature air, such as exhaust or displacement air, during withdrawal of the fluid 202 from the vial 205 or syringe. The material of the fluid channel 204 may comprise or be in direct contact with a thermally conductive metal material, including aluminum, copper, and stainless steel or other materials, having a thermal conductivity of about 45-385W/mK, to allow for more efficient heat exchange between the environment 201 and the cold fluid 202. The fluid channel 204 may also include a thermally conductive polymer having an enhanced thermal conductivity, such as 1-100W/mK. Further, as previously described, during the transfer process, thermal energy may be transferred to the cold fluid 202 by kinetic, frictional, and shear forces associated with the moving fluid.

Referring to fig. 92-93, for descriptive purposes, the fluid channel, generally identified by reference numeral 204, is shown in the form of a tube, but may also be a pre-formed fluid flow path molded as part of the transfer device, or in such other forms as may be preferred. As shown, the flow path portion 204A extends from the vial loading station or port to the transfer or pressure chamber C. The fluid or drug flow path portion 204B extends from the pressure chamber C to the inlet of the heat exchange member 207, which is optional. The thermally conductive member 207 may include a large mass 207 of any of the above-described metals or plastics with a geometry 208 to maximize the ratio of fluid surface area to volume, and may be part of or in contact with the material in the fluid path 204. The heat exchange member 207 may include multiple flow paths (see fig. 93) or a serpentine flow path, for example, to enhance contact between the fluid and the surface of the heat transfer member. The transfer device 203 may also contain additional heat exchange elements 207 to enhance heat exchange between the cold fluid 202 and the environment 201. A metal or plastic mesh at room temperature and/or a filter 209 may be located within the fluid channel 204 to enhance heat exchange between the cold fluid 202 and the environment 201. The cold fluid 202 may also be passed through a matrix of thermally conductive material, such as a matrix formed of stainless steel balls or other small elements within the fluid channel that allow high surface area to mass contact with the fluid. The fluid flow path 204C extends from the heat exchanger or conductor 207 to an inlet or fill port to fill an injection device, such as the injection device described in detail above.

The graph 100-102 is a graph depicting data from certain tests relating to the warming of a cryogenic fluid flowing through a transfer system and into an injection device similar to the injection device shown in one of the transfer and injection devices described above. Graph 100 illustrates the warming of a chilled water-based fluid, such as distilled water, as compared to the independent room temperature warming temperatures of similar fluids. Tests were conducted with a transfer device similar to the transfer device 203 shown in fig. 91-93 and an injection device 206 similar to the injection device shown in fig. 68-76. Transfer device 203 provides heat transfer from environment 201 to cold or frozen fluid 202 contained in vial 205, causing cold solution 202 to warm to near room temperature as it is transferred from vial 205 to injection device 206 through fluid path 204, greatly reducing the time required for the patient to wait for self-injection compared to a separately warmed vial.

Drugs that require refrigeration must typically be warmed to room temperature prior to administration. The transfer and injection apparatus described herein provides for relatively rapid fluid warming upon removal from the refrigerator without waiting for a separate warming of the drug vial at room temperature. More specifically, the graph 100 shows two data sets or graphs 280 and 282, temperature in degrees Celsius on the Y-axis and time in seconds on the X-axis. A first data set or graph 280 represents the independent warming of the water-based fluid contents of a standard glass vial 205, wherein the fluid contents 202 begin at or near 2-8 ℃. The vial contained 4cc of a simulated single injection dosage fluid with a room temperature viscosity of about 8 cP. Vial 205 is removed from the refrigerator and a temperature monitoring system is inserted into the vial to monitor the temperature of the solution. Thus, the vials are used as a control comparison to generally model or represent a standard frozen drug vial or a pre-filled injection system (e.g., a pre-filled syringe) that instructs the user to remove from the refrigerator and place (e.g., on a counter top) to gradually warm to room temperature prior to use. Graph 280 of graph 100 shows the normal first order temperature rise of the solution over time. As can be seen from graph 280, the temperature of the fluid in the vial required about 20 minutes (1200 seconds) to rise to 21 deg.C when removed from the freezer, with an average room temperature of about 23.8 deg.C

The second data set or graph 282 in fig. 100 originates from a second vial 205 in which the same volume of cold water-based fluid 202 is transferred and dispensed from a transfer device similar to 203 (but without the heat exchanger 207) and the injection device 206. Briefly, this attempts to generally simulate the process desired by the patient, including transferring the injectate from the vial, through the transfer device and into and dispensing from the injection device. The transfer device employs a PVC fluid flow tube 204 with an ID of about 0.05 inch (1.3mm), a flow path length from the vial to the rigid plastic pressure chamber C of about 4.86 inches (12.3cm), a flow path length from the pressure chamber C to a filter (not shown) of about 1.0 inch (2.54cm), and a flow path length from the filter into an expandable chamber or bladder in the injection device 206 of about 0.5 inch (1.27 cm). As previously described, the pressure chamber C is used to move the fluid in the vial through the transfer device and into the expandable member or bladder 78 of the injection device 206. Dispensing from the injection device is through a 30 gauge needle.

Referring to fig. 100, at time 0, the second vial 205 with cold fluid at 2-8 ℃ was removed from the refrigerator. Vial 205 is inserted into transfer device 203 to begin automated transfer. Cold fluid 202 is transferred from vial 205 through fluid channel 204, pressure chamber C, and into injection device 206. After the transfer is complete, the solution is dispensed from the injection device 206. The temperature monitoring system measures the output flow temperature of the fluid dispensed from the injection device 206. In graph 100, the dispensing begins at about t 80 seconds and completes at about t 270 seconds. As shown in graph 100, the fluid temperature is measured throughout the dispensing process.

As can be seen in figure 100, since the transfer by the transfer device 203 and into the injection device 206 both started at room temperature of about 23.8 ℃, the temperature of the dispensed fluid rose to about 21 ℃ within about 80 seconds after it had been removed from the refrigerator. Continuous measurements showed that the temperature of the dispensed solution was between 21 and 22 ℃ throughout the dispensing from start to finish. The time saved for the patient using the present system is approximately 18 minutes compared to simulating a standard frozen vial or frozen pre-filled system. The rate of temperature rise in the transfer apparatus and the injection device is on average about 10 times greater than the rate of temperature rise when heating using a separate environment. Since the steps of the present system are relatively continuous and without long delays, this should contribute significantly to patient compliance. In contrast, leaving the vial on the counter for 20 minutes until it warms up (e.g., during a separate ambient warming process) can cause the patient to forget or become distracted, which can easily lead to missed or untimely treatments or injections.

Tests were also conducted to simulate the system of fig. 88-90 and are reflected in fig. 101. As shown, the manual injector system 189 also provides heat transfer to the injection 196 in the injector 197 and allows the frozen drug or other solution to reach near room temperature before being dispensed from the injection device as it passes from the injector through the fluid passage 195 and into the injection device 7. The graph 101 shows two data sets or graphs 284 and 286, temperature in degrees c on the Y-axis and time in seconds on the X-axis. The first graph 284 is from a standard glass vial 205 having the same volume and viscosity (4cc, 8cP) of cold water-based fluid 202 as used in the data reported in figure 100, at or near the range of 2-8 ℃ when removed from the refrigerator. Vial 205 is removed and a temperature monitoring system is inserted into the vial to monitor the temperature of the solution. This is a control and simulation pre-filled system injection system in which the user is instructed to remove from the refrigerator and let it warm to room temperature before use. Graph 294 of fig. 101 shows a normal first-order warming of the solution over time, and shows that warming by exposure to room temperature of about 24.2 ℃ (e.g., simply resting on a counter in a room) takes about 23 minutes.

The second data set or graph 286 in fig. 101 is based on the removal of the injectate 196 from the manual fluid injector system 189 and the second vial 204 of cold fluid 202 of the same volume and viscosity that the injection device 7 transferred and dispensed, both starting at ambient room temperature of about 24.2 ℃. Referring to fig. 101, a room temperature standard syringe 197 made of rigid plastic is used to withdraw cold injection fluid 196 at 2-8 ℃ from a second vial 205, which is removed from the refrigerator at about time t-0. The syringe with injection fluid 196 is inserted into the manual syringe system 189 to begin the manual transfer. In fig. 89, cold injectate 196 is transferred from syringe 197 through fluid passage 195 into injection device 7. The solution or fluid is transferred from the syringe to the injection device through a standard PVC tube having an ID of about 0.050 inches (1.3mm) and a flow path length of about 3 inches (7.6cm) and into an expandable member or bladder 78 of the injection device. In practice, the flow path may also include check valves, filters, and the like.

After the transfer is complete, the solution is dispensed from the injection device 7. The temperature monitoring system measures the output flow temperature of the fluid dispensed from the injection device 7. As shown in fig. 101, the dispensing begins about 80 seconds after the vial is removed from the freezer. As shown in fig. 101, the temperature of the dispensed fluid was measured throughout the dispensing process, which was completed in about 350 seconds (5.8 minutes).

As can be seen in fig. 101, even when dispensed from the injection device, the fluid or solution is near room temperature and is between about 19 ℃ and 20 ℃ throughout the injection. The equivalent process of starting the dispense at the same temperature (19-20 c) in the case of a separately warmed-up simulated pre-filled system results in a time saving of about 13 minutes using the current system, as compared to the present embodiment.

Referring to fig. 88-90, repeated tests were performed on an injection fluid 196 stored in a syringe (not a vial) in a refrigerator. Fig. 102 shows two data sets or graphs 288 and 290, temperature (c) on the Y-axis and time (seconds) on the X-axis. The first data set or graph 288 is from a standard rigid plastic syringe 197 having a water-based injection fluid 196 (4cc volume, 8cP viscosity), such as distilled water, and stored in a refrigerator at or near 2-8 ℃. The syringe 197 with the injectate fluid 196 is removed and a temperature monitoring system is inserted into the syringe to monitor the temperature of the solution. This is a control and simulation pre-filled system injection system in which the user is instructed to take out of the refrigerator and let it out (e.g. on a counter) to warm to room temperature before use. In fig. 102, a first data set or graph 298 shows a normal first order temperature rise of the solution over time.

The second data set or graph 290 is derived by removing a second standard rigid plastic syringe 197, the syringe 197 having the same volume of water-based injectant fluid or solution 196 transferred and dispensed using the manual syringe system 189 and injection device 7, both starting at room temperature of about 24.2 ℃. Referring to fig. 102, the second syringe 197 with the injection 196 is removed from the refrigerator when t is 0. The syringe with the injection 196 is inserted into the manual syringe system 189 to begin the manual transfer. As shown in fig. 89, cold injectate 196 is transferred from syringe 197 through fluid passage 195 into injection device 7. The overall dimensions are as previously described for the use of the system. After the transfer is complete, the solution is dispensed from the injection device 7. The temperature monitoring system measures the output flow temperature of the fluid dispensed from the injection device 7. In fig. 102, this allocation begins at about t 80 seconds. As shown in fig. 102, the fluid temperature was measured throughout the dispensing process, which was about 17 c to 18 c, and was completed about 5 minutes after removing the frozen syringe from the refrigerator. Starting the equivalent dispense at about the same temperature (17-18℃.) in the case of a stand-alone ramped simulated pre-filled system results in a time savings of about 13 minutes for the current system compared to the current embodiment.

Radio frequency compliance monitoring

According to the National Committee for Patient Information and Education (NCPIE), the "lack of drug compliance is another drug problem in the united states. The lack of drug compliance (filling/refilling prescriptions on time) and compliance (taking prescriptions on time or prescription) by patients complicates the normal situation that could otherwise restore health. In addition, the lack of drug compliance and compliance adds significant cost to an already heavily burdened healthcare system, as well as increased medical expenses, doctor visits, and long term hospitalizations. Thus, the success of a drug in treating a condition depends on whether the prescription is filled and taken regularly as instructed. Currently, this is only the responsibility of the patient. However, even a good patient may accidentally forget to take or intentionally discontinue taking a medication when their symptoms begin to improve. Thus, for the reasons described above, an institution that alerts a patient, prescriber, healthcare provider, or another third party participant when non-compliance or non-compliance occurs would be very beneficial to allow intervention or alerting.

In accordance with other aspects of the present subject matter, when an injection is performed with an automatic injection device, it is desirable to know when to initially fill or refill the prescription of the injection device and whether the injection device is being used correctly and on time. Although many prescription drugs are tracked as they are filled using a special label, there are few options to confirm whether a patient actually takes a drug. As more and more medication is present in injection devices, the ability to automatically track prescription initiation is currently limited in use. Furthermore, there is no ability to automatically track whether the injection device is being used correctly.

As described herein, automated tracking of compliance and adherence is achieved wirelessly using RF (radio frequency) technology installed within or cooperatively associated with the transfer and/or injection devices described herein. Current technology allows the transmission of data using Radio Frequency Identification (RFID) to automatically identify and track tags or microcircuit chips attached to objects. As used herein, RF or RFID or RF tag or RF chip is used broadly and interchangeably and is intended to include wireless electronic tags or chips for transmitting data/information using any suitable wireless communication protocol or technology such as bluetooth or any other wireless technology.

The RF tag or chip may be active or passive. While both types use radio frequency energy communication between the tag or transponder and the reader, the method of powering the tag differs. Active RFID uses an internal power source (e.g., a battery) within or associated with the tag to continuously power the tag and its RF communication circuitry, while passive RFID relies on RF energy transferred from the reader to the tag to power the tag. In the present subject matter, the injection device or transfer package may include an RFID tag, may optionally include a power source for the tag and may be read or received by an external reader. In one embodiment, the RF tag or chip is removably associated with the injection device such that it can be physically removed from the injection device when the injection device is in use. This allows subsequent disposal of the injection device without the restrictions or restrictions that may be imposed if the label or chip remains as part of the injection device after use.

Referring to fig. 94-95, the injection device 210 may include an electronic RF tag or chip 211 to monitor the status of the injection device 210. For example, the RF tag 211 may broadcast to the external reader 212 (if active) or present (if passive, read by the external reader 212) information or status, such as "the injection device 210 has been prescribed", "the injection device 210 has been removed from its packaging", "the injection device 210 has been actuated" and/or "the injection device 210 has completed its dose". The RF tag reader may also be associated with or communicate with an on-site or off-site data collection facility, such as through a wireless or hard-wired connection, to allow for recording and compiling information regarding compliance.

Referring to fig. 94-95, the RF tag 211 may be used to monitor whether the injection device 210 has been activated or primed or has completed its dosage. The injection device 210 may include an active or passive Radio Frequency (RF) tag or chip 211 at any suitable location. As shown below, when used inside an injection device, the RF tag or chip 211 may be attached to the button 213 and slidably communicate with the spring plate 214 during the first and second positions of the button 213. When the RF tag 211 is in slidable communication with the leaf spring 214, the RF tag 211 may broadcast (if active) or present (if passive, read by the external reader 212) a first status to include an unused status. Upon activation of the injection device 210, the button 213 is pressed to the dispensing position. At the end of the dispense cycle, the button 213 unlocks from the second depth or dispense position (as shown in fig. 95) to move upward to a final or post-fire position. In this post-transmission position, the RF tag 211 may no longer be in contact with the spring tab 214, thereby allowing the state (second state) of the RF tag 211 to change. In this second state, RF tag 211 may broadcast (if active) or present (if passive, read by external reader 212) the second state to include a use state. Alternatively, the RF tag 211 may be deformed or altered when the injection device is used in such a way that upon interrogation, the RF tag 211 presents a "used" signature. For example, if an RF tag includes two coils connected by a conductor, the initial signature of tag 211 would be a "two-coil" signature. Once the tag 211 has been used, two separate coils produce different signatures if the conductor connecting the two coils is broken.

For regulatory and/or disposability reasons, it may be desirable to locate the radio frequency tag or chip outside of the injection device. For example, the RF tag or chip 211 may also be associated with another part of the transfer device or system, such as a condom or pull-tab 100 (see fig. 83), to activate the tag or chip at one or more selected points of operation of the transfer device and/or injection device. An active RF tag or chip may be located on the condom, for example, and configured such that removal of the condom to begin the injection procedure closes contact between the long-life battery and the tag or chip transmitter.

Referring to fig. 108-111, the RF chip or tag 211 within the injection device 210 may have two states: a standby or off state and an active or transmit state. Referring to fig. 108 and 110, the state can be changed by establishing or breaking contact between the battery 262 and the contact 263. This may be accomplished, for example, by configuring the safety release or pull tab 100 to prevent electrical contact between the battery 262 and the contacts 263 by spatial isolation when the pull tab 100 is in place on the injection device 210, as shown in fig. 110. As shown in fig. 111, upon removal of the tab 100, the battery 262 and the contact 263 come together to contact each other and make electrical contact. As a result, the RF tag starts to function. Furthermore, different actions related to the use of the transfer and/or injection device may be employed to make or break the contact. For example, when one action is taken, such as inserting a vial into the transfer device, the previously inactive RF tag or chip may be activated by closing contact between the battery and the chip or tag transmitter, and deactivated by another action, such as by breaking such contact after use of the injection device.

For further example, referring to fig. 96-98, transfer device 215 may include an RF tag 211 to track the use of transfer package 215. For example, the RF tag 211 may broadcast (if active) or present (if passive, read by the external reader 212) information to the external reader 212, such as-the transfer package 215 has been opened, the vial 216 has been inserted, the transfer package 215 has been activated, and/or the syringe 210 has been removed from the transfer package 215. Referring to fig. 97-98, in another embodiment, transfer device 215 may include a means for reading RF tag 211 within injection device 206. For example, in existing transfer packages 215, active RF transmission may occur upon insertion of a vial/syringe/cartridge 216 into the transfer device 215, or upon retraction of the locking blade 217, or upon removal of the syringe 210. An advantage of mounting the active transmitter 220 in the transfer device 215 is that there is more mounting space and/or power supply and the transmitter 220 need not reside on the syringe 210.

In addition to usage information, the RF tag or chip 211 may also transmit or communicate data related to the transfer or injection device. For example, the tag or chip may be configured with memory storage capacity to communicate the type of injection device, lot number, amount of fluid administered, drug identification, and other relevant information. FIG. 99 schematically illustrates one type of system that may be used with the present subject matter. As shown, the RF tag or chip 250 may be of the active type and, when activated, actively transmits relevant information to a local patient module 252 located near the patient and the injection device. For example, the patient module may be a wall-mounted or table-top device located in the patient's home for receiving monitoring information transmitted by an RF tag or chip associated with the injection device and/or transfer device. The patient module may also be a cellular phone or the like.

The patient module may include a memory that holds data such as patient identification and related information. The patient module, in turn, communicates with a data manager 254 in a suitable manner, such as WIFI, cellular communications, telephone, hard-wired link, etc., which data manager 254 may be any suitable data network or cloud storage device for receiving and/or storing data received from the patient module indicative of the status and/or usage of the injection device in relation to the particular identified patient information. The data manager will be accessible to medical personnel responsible for monitoring the patient's use of the injection device and the patient's compliance with any prescribed injection protocol. The data manager may also be configured to automatically relay patient compliance information to the appropriate medical personnel, such as a particular doctor or clinic 256.

Compliance monitoring devices, systems, and methods, as well as other aspects of use with injection devices such as those described herein, are shown in fig. 105-114. As shown therein, the system may include a wireless (e.g., bluetooth) source, such as a battery-powered transmitting unit (e.g., microchip), indicated at 262 in fig. 107. The sending unit may be mounted in any suitable location and may be associated with or attached to a part of the injection device (and/or transfer device) such that it may be separated from the injection device or transfer device at the time of disposal — most injection device or transfer device structures may be recycled as the electronic circuitry and electronic chip are typically not similarly recyclable.

In some embodiments, the contact ring is disposed in the top of the injection device housing and is prevented from contacting the sense lead (which is attached to the injection device button) when the safety strip is installed. When the safety bar is removed, the contact ring of the housing contacts the sensing leads of the button. Different sequences of injection procedures can then be tracked based on the connection status between the contactor loop and the sense lead (i.e., the position of the contactor loop relative to the sense lead). Infrared sensors may also be embedded in the injection device to optically track the progress of delivery, for example, by monitoring the location or amount of injection fluid in an expandable member of the injection device.

Referring to fig. 108 and 109, an embodiment of an RF tag or chip 211 includes the following components: battery 262, contacts 263, bluetooth module/microprocessor 265, button sensor 267, and antenna 269. Battery 262 provides stored energy to power the system. This can be a button cell or equivalent in the 1.5-3V voltage range with a power output of 5-100 mAh. As previously described, contacts 263 provide an electrical connection between battery 262 and RF tag or chip 211. The contacts 263 are configured to interact with the pull tab 100 until no electrical contact is allowed until the time of use when the user removes the pull tab 100. Bluetooth module 265 has an integrated microprocessor. An example of a suitable bluetooth module is the analog Semiconductor part number DA14580-01 UNA. In an alternative embodiment, the bluetooth module may be separate from the microprocessor.

Fig. 112 and 113 show a button position sensing system in an embodiment of the device. The sensing system uses an infrared transmitter and receiver sensor combination 267. The RF chip 211 is mounted to the underside surface of the device button 177 with the sensor 267 facing down. The reflective member 112 is mounted in a fixed manner to the bottom of the injection device. When the device button is actuated to move from the upward raised or extended position shown in fig. 112 to the downward lowered or retracted position shown in fig. 113, the sensor 267 detects a decrease in distance from the reflective member 112. Conversely, when the button is released to move from the position of fig. 113 to the position of fig. 112 after delivery of the drug, the sensor 267 detects an increase in distance from the reflective member 112. The sensor 267 sends this button position information to the microprocessor module 265.

Fig. 114 shows the processing performed by the microprocessor module 265 in the embodiment of the apparatus. When the microprocessor is powered up, the start timer indicated at block 302 is started, such as by removing security patch 100 as described above with reference to fig. 110 and 111. The mode or state of the device is then set to "ready to transmit" (i.e., ready to dispense) as shown in block 304, and a bluetooth packet indicating the mode of the device is sent to a bluetooth-enabled remote reader or receiver (such as 212 of fig. 94-96), which may be a smart phone or computer system by way of example only. The pattern is displayed to the user on the remote receiver.

The process of block 308a is then performed to conserve battery life of the device.

The microprocessor then checks the position of the device button (177 in fig. 112 and 113) using, for example, the IR sensor described above with reference to fig. 112 and 113, as shown in block 312. As shown at 314, if the device button has not been pressed to the down position, the above process is repeated. If the device button has been pressed, the start time for injection delivery is recorded, as shown in block 316, and the device mode is set to "dispense", as shown in block 318. The pattern is transmitted to the remote receiver where it is displayed to the user, as shown at block 322.

The process of block 308b is then performed to conserve battery life of the device by intermittently or alternately placing the processor in a low energy sleep mode and then waking the processor at one second (or other suitable time) intervals.

The microprocessor then checks the position of the device button as indicated in block 324. If the device button has not returned to the raised or up position, as indicated at 326, the above process from block 322 is repeated. If the device button has been moved to the up position, the end time for the injection delivery is recorded, as shown in block 332, and the device mode is set to "complete", as shown in block 334. The pattern is transmitted to the remote receiver where it is displayed to the user, as shown in block 336.

The process of block 308c is then performed to conserve battery life of the device, after which the "complete" status of the device is again sent to the remote receiver (block 336).

Embodiments of the present disclosure may provide "smart" connected devices that enable patients to self-administer high volume/viscosity medications, thereby enabling and facilitating freedom and mobility of the patients. Embodiments may provide a safe, simple, and discreet drug delivery experience for a user.

Embodiments of the present disclosure may provide an intelligent device system to provide three pieces of information about the operation of a drug delivery system: 1) when the device is powered on; 2) when the device has started to deliver; and 3) when the transfer has been completed. In some embodiments, the user interaction is simple; the user opens the application on his handset, the rest will be done by the smart device. There are no other steps using the device.

Embodiments of the present disclosure may provide advantages such as:

small circuit board footprint-the entire electronics package fits inside the existing button and is less than 3/8 inches (9.5mm) in diameter. This allows easy removal of the electronic device (button) for electronic disposal and recycling.

Button cell, a simple, well-known power source, has a long service life and shelf life. The battery is isolated from the electronic device by a safety strip prior to the time of use. The user removing the security bar activation circuit while in use;

embedded microprocessor based systems for low power consumption and small footprint; and/or

The Bluetooth low-power transmission is used for low power consumption, and makes full use of the universality of the mobile phone close to a user.

In 2015, the percentage of the population in developed countries with smartphones was 68%. To take advantage of this existing platform, embodiments of the present disclosure may utilize bluetooth communications to provide data to a user. Further, embodiments may integrate Bluetooth Low Energy (BLE) into the device. BLE is a newer version of the bluetooth specification, has been introduced in bluetooth v4.0, and has been widely adopted in wearable fitness sensors and the like. BLE is designed specifically for low power, low cost applications that require lower data throughput rates than traditional bluetooth connections (e.g., audio streaming or hands-free telephone connections).

Two main types of connection are defined in the bluetooth standard: a standard (binding) mode and a broadcast (also referred to as "beacon") mode. In a standard or binding connection, the host (smartphone with an installed application) will create a saved connection with the peripheral (i.e., smart device). In this case, through the pairing process, both the host and the peripheral device share data to create a permanent connection that allows sharing between only one host and one peripheral device. The advantage of this approach is a secure connection, allowing the exchange of encrypted information that cannot be decoded without the encryption key. However, the main drawback of this approach is that the pairing process can be cumbersome, requiring user interaction and increased power consumption of the peripheral devices, since both the receiving and transmitting radios require communication power.

In broadcast mode (also referred to as "beacons"), the peripheral transmits data at regular intervals, which can be read by any nearby host. In this case, the peripheral device broadcasts only data; data is never received. This mode has several advantages:

powering only the transmitting radio on the peripheral device, thereby reducing power consumption;

further power savings may be achieved by a lower power "sleep" mode, since the peripheral device does not need to "listen" for data from the host device, waking up only when new data needs to be broadcast;

furthermore, since the peripheral device is a send-only device, enhanced security is provided because the hardware cannot be "hijacked" or loaded with malware. This reduces or eliminates the risk of unauthorized remote control of the device. The software has been loaded onto the device at the factory to prevent unauthorized changes after deployment.

Other bluetooth enabled devices may also "listen" to the broadcast from the smart device, although without the appropriate application installed, but the data will only include a list of unusable binary, lacking any text or other readable identification. Thus, a lack of encrypted connections does not expose any sensitive user information. The data also never contains any identifying patient information, such as name or identification number (HIPAA company), that may be relevant to a particular individual.

An important attribute of the connected healthcare implementation within embodiments of the present disclosure may be that it does not affect the basic performance functionality of the drug delivery device. In some embodiments, this feature of the device only reports the status of the device and never changes the function of the drug delivery device. Some embodiments of the device will complete the delivery of the drug and provide visual feedback to the user regarding the status of the device even in the event of a serious failure of a bluetooth component, such as a battery.

With the bluetooth low energy broadcast mode and through a tiny electronic chip in the device button, some embodiments of the present disclosure can deliver real-time device performance information in small, low-cost, convenient packages.

The present subject matter has been described in terms of specific embodiments, which are for purposes of illustration only and are not limiting. It is to be understood that the scope of the present subject matter is not limited to only the illustrated embodiments or equivalents thereof but has broader application in varying configurations and uses, some of which may be apparent upon reading this specification and others which may become apparent only after certain research and/or development.

Claims (20)

1. An injection device comprising:

a. a housing;

b. a drug reservoir disposed in the housing;

c. an injection cannula movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir;

d. a microprocessor mounted on or within the housing;

e. a sensor system in communication with the microprocessor, the sensor system configured to detect when the infusion cannula is in the pre-dispense position and when the cannula is in the dispense position;

f. a transmitter in communication with the microprocessor, the transmitter configured to transmit data indicative of the cannula position to a remote receiver.

2. The injection device of claim 1, further comprising a mechanism positioned within the housing and configured to move the cannula between a pre-dispense position and a dispense position, and wherein the sensor system is operably connected to the mechanism.

3. The injection device of claim 2, wherein the mechanism comprises a button configured such that the cannula moves from a pre-dispense position to a dispense position when the button is depressed, and wherein the sensor is operably connected to the button.

4. The injection device of claim 3, wherein the sensor system comprises: an infrared transmitter and an infrared receiver mounted on the button; and a reflection member mounted on the housing to be fixed with respect to a position of the button.

5. The injection device of claim 4, wherein the infrared transmitter and infrared receiver are mounted on an underside of the button.

6. The injection device of any one of claims 4 and 5, wherein the button moves between an extended position relative to the housing when the cannula is in a pre-dispense position and a retracted position relative to the housing when the cannula is in a dispense position.

7. The injection device of claim 6, wherein the mechanism is configured to automatically return the button to the extended position upon completion of dispensing of the medicament.

8. The injection device of claim 1, further comprising:

f. an electronic chip, wherein the electronic chip comprises a microprocessor, a battery and contacts, the battery supplying power to the microprocessor when electrical contact is made between the battery and the contacts; and

g. a pull tab removably positioned between the battery and the contact to avoid electrical contact between the battery and the contact.

9. The injection device of claim 1, wherein the microprocessor and transmitter are combined into a single component.

10. The injection device of claim 1, wherein the transmitter is a bluetooth transmitter.

11. A drug delivery system for transferring and administering an injection liquid drug into a subject, comprising a transfer device and an injection apparatus; the transfer apparatus comprises an injection device docking station; and

a wireless signal transmitting unit carried by the transfer apparatus and/or injection device.

12. The delivery system of claim 11, the transmitting unit further comprising a radio frequency tag containing data identifying the system, wherein the radio frequency tag is an active radio frequency tag configured to signal activation of the injection device and completion of injection by the injection device.

13. The delivery system of claim 11, wherein the wireless signal transmitting unit is configured for low power transmission in accordance with the bluetooth low energy specification.

14. The delivery system of claim 11, further comprising a button battery and circuitry configured to cause the button battery to power the wireless signaling unit.

15. The delivery system of claim 11, wherein the injection device comprises a button for activating the injection device, and wherein the wireless signal transmitting unit is located within the button.

16. The delivery system of claim 11, wherein the wireless signal transmitting unit comprises a microprocessor.

17. The delivery system of claim 11, wherein the wireless signaling unit has a diameter of less than about 3/8 inches or 9.5 mm.

18. A method for monitoring use of an injection device, comprising the steps of:

a. sensing a position of a cannula of an injection device;

b. data indicative of the cannula position is transmitted to a remote receiver.

19. The method of claim 18, further comprising the steps of: detecting when power is provided to circuitry of the device, wherein the circuitry comprises a microprocessor and a transmitter.

20. The method of claim 18, wherein step a comprises monitoring a position of a button for actuating an injection cannula of the injection device.

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